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Early hypoxemia burden is strongly associated with severe intracranial hemorrhage in preterm infants

Journal of Perinatology volume 39, pages 48–53 (2019)Cite this article

Subjects

Abstract

Objectives:

The objective of this study was to define the association between the burden of severe hypoxemia (SpO2 ≤70%) in the first week of life and development of severe ICH (grade III/IV) in preterm infants.

Study design:

Infants born at <32 weeks or weighing <1500 g underwent prospective SpO2 recording from birth through 7 days. Severe hypoxemia burden was calculated as the percentage of the error-corrected recording where SpO2 ≤70%. Binary logistic regression was used to model the relationship between hypoxemia burden and severe ICH.

Results:

A total of 163.3 million valid SpO2 data points were collected from 645 infants with mean EGA = 27.7 ± 2.6 weeks, BW = 1005 ± 291 g; 38/645 (6%) developed severe ICH. There was a greater mean hypoxemia burden for infants with severe ICH (3%) compared to those without (0.1%) and remained significant when controlling for multiple confounding factors.

Conclusion:

The severe hypoxemia burden in the first week of life is strongly associated with severe ICH.

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References

  1. Stoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh MC, et al. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics. 2010;126:443–56.

    Article  Google Scholar 

  2. Wilson-Costello D, Friedman H, Minich N, Fanaroff AA, Hack M. Improved survival rates with increased neurodevelopmental disability for extremely low birth weight infants in the 1990s. Pediatrics. 2005;115:997–1003.

    Article  Google Scholar 

  3. Jain NJ, Kruse LK, Demissie K, Khandelwal M. Impact of mode of delivery on neonatal complications: trends between 1997 and 2005. J Matern Fetal Neonatal Med. 2009;22:491–500.

    Article  Google Scholar 

  4. Ment LR, Duncan CC, Ehrenkranz RA, Lange RC, Taylor KJ, Kleinman CS, et al. Intraventricular hemorrhage in the preterm neonate: timing and cerebral blood flow changes. J Pediatr. 1984;104:419–25.

    Article  CAS  Google Scholar 

  5. Ment LR, Ehrenkranz RA, Lange RC, Rothstein PT, Duncan CC. Alterations in cerebral blood flow in preterm infants with intraventricular hemorrhage. Pediatrics. 1981;68:763–9.

    CAS  PubMed  Google Scholar 

  6. Soul JS, Hammer PE, Tsuji M, Saul JP, Bassan H, Limperopoulos C, et al. Fluctuating pressure-passivity is common in the cerebral circulation of sick premature infants. Pediatr Res. 2007;61:467–73.

    Article  Google Scholar 

  7. Vesoulis ZA, Liao SM, Trivedi SB, Ters NE, Mathur AM. A novel method for assessing cerebral autoregulation in preterm infants using transfer function analysis. Pediatr Res. 2016;79:453–9.

    Article  CAS  Google Scholar 

  8. Alderliesten T, Lemmers PMA, Smarius JJM, van de Vosse RE, Baerts W, van Bel F. Cerebral oxygenation, extraction, and autoregulation in very preterm infants who develop peri-intraventricular hemorrhage. J Pediatr. 2013;162:698–704. e2

    Article  Google Scholar 

  9. Granger DN, Kvietys PR. Reperfusion injury and reactive oxygen species: The evolution of a concept. Redox Biol. 2015;6:524–51.

    Article  CAS  Google Scholar 

  10. Ballabh P. Intraventricular hemorrhage in premature infants: mechanism of disease. Pediatr Res. 2010;67:1–8.

    Article  Google Scholar 

  11. Volpe JJ. Neurology of the newborn. 5th ed. Philadelphia: Saunders/Elsevier; 2008. p. 1094.

    Google Scholar 

  12. Chen J, Smith LEH. Retinopathy of prematurity. Angiogenesis. 2007;10:133–40.

    Article  Google Scholar 

  13. Gogate P, Gilbert C, Zin A. Severe visual Impairment and blindness in infants: causes and opportunities for control. Middle East Afr J Ophthalmol. 2011;18:109.

    Article  Google Scholar 

  14. BOOST II United Kingdom Collaborative Group, BOOST II Australia Collaborative Group, BOOST II New Zealand Collaborative Group, Stenson BJ, Tarnow-Mordi WO, Darlow BA, et al. Oxygen saturation and outcomes in preterm infants. N Engl J Med. 2013;368:2094–104.

    Article  Google Scholar 

  15. Supplemental therapeutic oxygen for prethreshold retinopathy of prematurity (STOP-ROP), a randomized, controlled trial. I: primary outcomes. Pediatrics. 2000;105:295–310.

  16. Sears JE, Pietz J, Sonnie C, Dolcini D, Hoppe G. A change in oxygen supplementation can decrease the incidence of retinopathy of prematurity. Ophthalmology. 2009;116:513–8.

    Article  Google Scholar 

  17. Askie LM, Darlow BA, Davis PG, Finer N, Stenson B, Vento M. et al. Effects of targeting lower versus higher arterial oxygen saturations on death or disability in preterm infants. Cochrane Database Syst Rev. 2017;4:CD011190

    PubMed  Google Scholar 

  18. SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network, Carlo WA, Finer NN, Walsh MC, Rich W, Gantz MG, et al. Target ranges of oxygen saturation in extremely preterm infants. N Engl J Med. 2010;362:1959–69.

    Article  Google Scholar 

  19. Hyttel-Sorensen S, Pellicer A, Alderliesten T, Austin T, van Bel F, Benders M, et al. Cerebral near infrared spectroscopy oximetry in extremely preterm infants: phase II randomised clinical trial. BMJ. 2015;350:g7635.

    Article  Google Scholar 

  20. Collins J-A, Rudenski A, Gibson J, Howard L, O’Driscoll R. Relating oxygen partial pressure, saturation and content: the haemoglobin–oxygen dissociation curve. Breathe. 2015;11:194–201.

    Article  Google Scholar 

  21. Madan A. Correlation between the levels of SpO2and PaO2. Lung India Organ Indian Chest Soc. 2017;34:307–8.

    Google Scholar 

  22. Martin RJ, Fanaroff AA, Walsh MC. Fanaroff and Martin’s neonatal-perinatal medicine: diseases of the fetus and infant. Philadelphia: Saunders/Elsevier; 2011.

    Google Scholar 

  23. Jay Goldsmith, Edward Karotkin, Gautham Suresh, Martin Keszler. Assisted ventilation of the neonate. St. Louis: Elsevier/Saunders; 2011.

  24. Bolivar JM, Gerhardt T, Gonzalez A, Hummler H, Claure N, Everett R, et al. Mechanisms for episodes of hypoxemia in preterm infants undergoing mechanical ventilation. J Pediatr. 1995;127:767–73.

    Article  CAS  Google Scholar 

  25. Shiao SY, Ou CN. Validation of oxygen saturation monitoring in neonates. Am J Crit Care. 2007;16:168–78.

    PubMed  PubMed Central  Google Scholar 

  26. Sullivan BA, Wallman-Stokes A, Isler J, Sahni R, Moorman JR, Fairchild KD, Lake DE. Early Pulse Oximetry Data Improves Prediction of Death and Adverse Outcomes in a Two-Center Cohort of Very Low Birth Weight Infants. Am J Perinatol. 2018 May 28. https://doi.org/10.1055/s-0038-1654712. [Epub ahead of print] PubMed PMID: 29807371.

  27. Kumar NPD, Praveena B. Mortality profile and timing of death in extremely low birth weight infants from 2013 to 2015 admitted to neonatal intensive care unit, Government General Hospital, Anantapur. Int J Sci Study. 2016;4:114–7.

    Google Scholar 

  28. Barton L, Hodgman JE, Pavlova Z. Causes of death in the extremely low birth weight infant. Pediatrics. 1999;103:446–51.

    Article  CAS  Google Scholar 

  29. Sjostedt S, Rooth G. Low oxygen tension in the management of newborn infants. Arch Dis Child. 1957;32:397–400.

    Article  CAS  Google Scholar 

  30. Harris AP, Sendak MJ, Chung DC, Richardson CA. Validation of arterial oxygen saturation measurements in utero using pulse oximetry. Am J Perinatol. 1993;10:250–4.

    Article  CAS  Google Scholar 

  31. Poets CF, Roberts RS, Schmidt B, Whyte RK, Asztalos EV, Bader D, et al. Association between intermittent hypoxemia or bradycardia and late death or disability in extremely preterm infants. JAMA. 2015;314:595.

    Article  CAS  Google Scholar 

  32. Ballabh P, Xu H, Hu F, Braun A, Smith K, Rivera A, et al. Angiogenic inhibition reduces germinal matrix hemorrhage. Nat Med. 2007;13:477–85.

    Article  CAS  Google Scholar 

  33. Mu D, Jiang X, Sheldon RA, Fox CK, Hamrick SEG, Vexler ZS, et al. Regulation of hypoxia-inducible factor 1alpha and induction of vascular endothelial growth factor in a rat neonatal stroke model. Neurobiol Dis. 2003;14:524–34.

    Article  CAS  Google Scholar 

  34. Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ, Holash J. Vascular-specific growth factors and blood vessel formation. Nature. 2000;407:242–8.

    Article  CAS  Google Scholar 

  35. Braun A, Xu H, Hu F, Kocherlakota P, Siegel D, Chander P, et al. Paucity of pericytes in germinal matrix vasculature of premature infants. J Neurosci. 2007;27:12012–24.

    Article  CAS  Google Scholar 

  36. Ballabh P, Hu F, Kumarasiri M, Braun A, Nedergaard M. Development of tight junction molecules in blood vessels of germinal matrix, cerebral cortex, and white matter. Pediatr Res. 2005;58:791–8.

    Article  CAS  Google Scholar 

  37. El-Khoury N, Braun A, Hu F, Pandey M, Nedergaard M, Lagamma EF, et al. Astrocyte end-feet in germinal matrix, cerebral cortex, and white matter in developing infants. Pediatr Res. 2006;59:673–9.

    Article  Google Scholar 

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Acknowledgements

The authors wish to acknowledge the contributions of Ryan Colvin, Amy Distler, Gina Myers (WU), and Marilyn Weindler (CUMC) for their assistance in identifying patient records and data collection.

Funding

This work was supported by the following grants: Washington University Institute of Clinical and Translational Sciences KL2 Training Program (NIH/NCATS KL2 TR000450); The Barnes-Jewish Hospital Foundation and the Washington University Institute of Clinical and Translational Sciences Clinical and Translational Funding Program (NIH/NCATS UL1 TR000448); Washington University in St. Louis Center for Biomedical Informatics, Clinical Investigation Data Exploration Repository (NIH/NCATS UL1 TR000448); and the National Institutes of Health, grant numbers HD072071 and HL133708.

Author information

Authors and Affiliations

  1. Division of Newborn Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA

    Zachary A. Vesoulis, Rachel L. Bank & Amit M. Mathur

  2. Department of Medicine, University of Virginia, Charlottesville, VA, USA

    Doug Lake & J. Randall Moorman

  3. Department of Pediatrics, Columbia University, New York, NY, USA

    Aaron Wallman-Stokes, Rakesh Sahni & Joseph R. Isler

  4. Department of Pediatrics, University of Virginia, Charlottesville, VA, USA

    Karen D. Fairchild

Authors
  1. Zachary A. Vesoulis
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  2. Rachel L. Bank
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Correspondence to Zachary A. Vesoulis.

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Vesoulis, Z.A., Bank, R.L., Lake, D. et al. Early hypoxemia burden is strongly associated with severe intracranial hemorrhage in preterm infants. J Perinatol 39, 48–53 (2019). https://doi.org/10.1038/s41372-018-0236-2

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  • DOI: https://doi.org/10.1038/s41372-018-0236-2

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