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Original Investigation
June 4, 2018

Association Between Early Caffeine Citrate Administration and Risk of Acute Kidney Injury in Preterm Neonates: Results From the AWAKEN Study

Author Affiliations
  • 1Division of Neonatology, Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin–Madison
  • 2Division of Nephrology, Department of Pediatrics, The University of Alabama at Birmingham
  • 3Division of Nephrology, Department of Pediatrics, Eastern Virginia Medical School, Norfolk
  • 4Division of Neonatology, Department of Pediatrics, Golisano Children’s Hospital, University of Rochester, Rochester, New York
  • 5Division of Nephrology, Department of Pediatrics, C.S. Mott Children’s Hospital, University of Michigan, Ann Arbor
  • 6Division of Neonatology, Department of Pediatrics, University of Virginia, Charlottesville
  • 7Division of Nephrology, Department of Pediatrics, University of Virginia, Charlottesville
JAMA Pediatr. 2018;172(6):e180322. doi:10.1001/jamapediatrics.2018.0322
Key Points

Question  Is early caffeine citrate administration associated with reduced incidence or severity of acute kidney injury in preterm neonates?

Findings  In this multicenter cohort study of 675 preterm neonates, those who received caffeine in the first 7 days after birth developed acute kidney injury less frequently than neonates who did not (11.2% vs 31.6%).

Meaning  Caffeine administration in the first 7 days after birth may be associated with less frequent acute kidney injury in preterm neonates; further studies on dosage, the timing of administration, and long-term outcomes are needed.

Abstract

Importance  Acute kidney injury (AKI) occurs commonly in preterm neonates and is associated with increased morbidity and mortality.

Objectives  To examine the association between caffeine citrate administration and AKI in preterm neonates in the first 7 days after birth and to test the hypothesis that caffeine administration would be associated with reduced incidence and severity of AKI.

Design, Setting, and Participants  This study was a secondary analysis of the Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) study, a retrospective observational cohort that enrolled neonates born from January 1 to March 31, 2014. The dates of analysis were October 2016 to December 2017. The setting was an international, multicenter cohort study of neonates admitted to 24 participating level III or IV neonatal intensive care units. Participants met the original inclusion and exclusion criteria of the AWAKEN study. Additional exclusion criteria for this study included participants greater than or equal to 33 weeks’ gestation at birth, admission after age 7 days, use of theophylline in the neonatal intensive care unit, or lack of data to define AKI. There were 675 preterm neonates available for analysis.

Exposure  Administration of caffeine in the first 7 days after birth.

Main Outcomes and Measures  The primary outcome was the incidence of AKI (based on the modified neonatal Kidney Disease: Improving Global Outcomes [KDIGO] definition) in the first 7 days after birth. The hypothesis that caffeine administration would be associated with reduced AKI incidence was formulated before data analysis.

Results  The study cohort (n = 675) was 55.4% (n = 374) male, with a mean (SD) gestational age of 28.9 (2.8) weeks and a mean (SD) birth weight of 1285 (477) g. Acute kidney injury occurred in 122 neonates (18.1%) in the first 7 days after birth. Acute kidney injury occurred less frequently among neonates who received caffeine than among those who did not (50 of 447 [11.2%] vs 72 of 228 [31.6%], P < .01). After multivariable adjustment, administration of caffeine remained associated with reduced odds of developing AKI (adjusted odds ratio, 0.20; 95% CI, 0.11-0.34), indicating that for every 4.3 neonates exposed to caffeine one case of AKI was prevented. Among neonates with early AKI, those receiving caffeine were less likely to develop stage 2 or 3 AKI (adjusted odds ratio, 0.20; 95% CI, 0.12-0.34).

Conclusions and Relevance  Caffeine administration in preterm neonates is associated with reduced incidence and severity of AKI. Further studies should focus on the timing and dosage of caffeine to optimize the prevention of AKI.

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