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Association of early dysnatremia with mortality in the neonatal intensive care unit: results from the AWAKEN study

Abstract

Objective

To determine the association of dysnatremia in the first postnatal week and risk of acute kidney injury (AKI) and mortality.

Study design

A secondary analysis of 1979 neonates in the AWAKEN cohort evaluated the association of dysnatremia with (1) AKI in the first postnatal week and (2) mortality, utilizing time-varying Cox proportional hazard models.

Result

Dysnatremia developed in 50.2% of the cohort and was not associated with AKI. Mortality was associated with hyponatremia (HR 2.15, 95% CI 1.07–4.31), hypernatremia (HR 4.23, 95% CI 2.07–8.65), and combined hypo/hypernatremia (HR 6.39, 95% CI 2.01–14.01). In stratified models by AKI-status, hypernatremia and hypo/hypernatremia increased risk of mortality in neonates without AKI.

Conclusion

Dysnatremia within the first postnatal week was associated with increased risk of mortality. Hypernatremia and combined hypo/hypernatremia remained significantly associated with mortality in neonates without AKI. This may reflect fluid strategies kidney injury independent of creatinine and urine-output defined AKI, and/or systemic inflammation.

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Fig. 1: Flowchart of inclusion and exclusion criteria.
Fig. 2: Risk of dynatremia and mortality.

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Acknowledgements

The authors thank all the members of the Neonatal Kidney Collaborative who participated in the AWAKEN study: University of Alabama, Birmingham: David Askenazi, MD; Namasivayam Ambalavanan, MD; Russell Griffin, PhD; Cincinnati Children’s Hospital: Stuart Goldstein, MD; Amy Nathan, MD; James Greenberg, MD; Canberra Hospital: Alison Kent, MD (currently at the University of Rochester); Jeffrey Fletcher, MD; Farah Sethna, MD; Children’s Hospital of Colorado: Danielle Soranno, MD; Jason Gien, MD; Katja Gist, MD; Children’s Hospital at Montefiore/Albert Einstein: Mamta Fuloria, MD; Kim Reidy, MD; Frederick Kaskel, MD; Natalie Uy, MD; Children’s National Medical Center: Mary Revenis, MD; Sofia Perrazo, MD; Shantanu Rastogi, MD; Golisano Children’s Hospital University of Rochester: George Schwartz, MD; Carl T. D’Angio, MD; Ronnie Guillet, MD, PhD; Erin Rademacher, MD; Ahmed El Samra, MD (currently Union Hospital, Terre Haute); Ayesa Mian, MD; Maimonides Medical Center: Juan Kupferman, MD; Alok Bhutada, MD; McGill University: Michael Zappitelli, MD; Pia Wintermark, MD; Medanta, Medicity The Cradle: Sanjay Wazir, MD; Sidharth Sethi, MD; Sandeep Dubey, MD; Metrohealth Medical Center: Maroun Mhanna, MD; Deepak Kumar, MD; Rupesh Raina, MD; Nationwide Children’s Hospital: Susan Ingraham, MD; Arwa Nada, MD; Elizabeth Bonachea, MD; Stonybrook University: Richard Fine, MD; Robert Woroniecki, MD; Shanthy Sridhar, MD; Texas Children’s Hospital: Ayse Ariken, MD; Christopher Rhee, MD; Tufts Medical Center: Lawrence Milner, MD; Alexandra Smith, MD; Julie Nicoletta, MD; University of British Columbia: Cherry Mammen, MD; Avash Jeet Singh, MD; Anne Synnes, MD; University of Iowa: Jennifer Jetton, MD; Tarah Colaizy, MD; Jonathan Klein, MD; Patrick Brophy (currently University of Rochester); University of Kentucky: Aftab Chishti, MD; Mina Hanna, MD; University of Miami: Carolyn Abitbol, MD; Marissa Defreitas, MD; Shahnaz Duara, MD; Salih Yasin, MD; University of Michigan: David Selewski, MD (currently Medical University of South Carolina); Subrata Sarker, MD; University of New Mexico: Craig Wong, MD; A. Staples, MD; Robin Ohls, MD; Catherine Joseph, MD (currently Texas Children’s Hospital); Tara Dupont, MD (currently University of Utah); University of Virginia: Jennifer Charlton, MD; Jonathan R. Swanson, MD; Matthew Harer (currently University of Wisconsin); Patricio Ray, MD; University of Washington: Sangeeta Hingorani, MD; Christine Hu, MD; Sandra Juul, MD.

Funding

This study was supported by the NIH T32 NIDDK 5T32DK007110- 46 and NIH/NCATS Einstein-Montefiore CTSA Grant UL1TR002556. Cincinnati Children’s Hospital Center for Acute Care Nephrology provided funding to create and maintain the Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) study Medidata Rave electronic database. The Pediatric and Infant Center for Acute Nephrology (PICAN) provided support for web meetings and for the Neonatal Kidney Collaborative (NKC) steering committee annual meeting at The University of Alabama at Birmingham (UAB). PICAN is part of the Department of Pediatrics at UAB and is funded by Children’s of Alabama hospital, UAB Department of Pediatrics, UAB School of Medicine, and UAB Center for Clinical and Translational Sciences (National Institutes of Health grant UL1TR001417). The AWAKEN study at The University of New Mexico was supported by the Clinical and Translational Science Center at The University of New Mexico (National Institutes of Health grant UL1TR001449) and by The University of Iowa Institute for Clinical and Translational Science (grant U54TR001356). The AWAKEN study investigators at the Canberra Hospital at the Australian National University Medical School were supported by the Canberra Hospital Private Practice Fund, and investigators at University of Virginia Children’s Hospital were supported by a 100 Women Who Care Grant from the 100 Women Charitable Foundation.

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Contributions

AB, KJR, FK, JC, DA contributed to the conception of the study. AB, RG, KJR, JC, DA, KG, RG, DS to the study design and interpretation of the results. AB and RG analyzed the data. AB wrote the manuscript with input from all authors. All authors provided critical feedback of the study design, analysis and manuscript.

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Correspondence to Abby M. Basalely.

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Competing interests

AMB has consulted for impact communication partners. KJR is site investigator for Advicenne and Travere Therapeutics clinical trials unrelated to this study. JRC is co-owner of Sindri Technologies LLC. DJA declares no real or perceived conflicts of interest that could affect the study design, collection, analysis and interpretation of data, writing of the report, or the decision to submit for publication. He does have the following commitments and funding sources that are not directly related to this study: DJA serves on the speaker board for Baxter (Baxter, USA), and the Acute Kidney Injury (AKI) Foundation (Cincinnati, OH, USA). DJA is a consultant for CHF solutions, and Medtronic.

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Basalely, A.M., Griffin, R., Gist, K.M. et al. Association of early dysnatremia with mortality in the neonatal intensive care unit: results from the AWAKEN study. J Perinatol 42, 1353–1360 (2022). https://doi.org/10.1038/s41372-021-01260-x

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