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Author Notes:

P. Brian Smith, MD, MPH, MHS, Box 17969, DCRI, Durham, NC 27715; phone 919-668-8951; brian.smith@duke.edu.

We would like to acknowledge Sofia Aliaga and Bradley Yoder for their input on data interpretation and manuscript development.

The authors declare no conflicts of interest.


Research Funding:

Supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (UL1TR000454 and KL2TR000455 to R.P.); and the Eunice Kennedy Shriver National Institutes of Child Health and Human Development (1K23HD060040-01); the American Recovery and Reinvestment Act (1R18AE000028-01 to P.S.); and the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH; UL1TR001117).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Pediatrics

Trends in Caffeine Use and Association between Clinical Outcomes and Timing of Therapy in Very Low Birth Weight Infants


Journal Title:

Journal of Pediatrics


Volume 164, Number 5


, Pages 992-+

Type of Work:

Article | Post-print: After Peer Review


Objective: To examine the effect of early initiation of caffeine therapy on neonatal outcomes and characterize the use of caffeine therapy in very low birth weight (VLBW) infants. Study design: We analyzed a cohort of 62 056 VLBW infants discharged between 1997 and 2010 who received caffeine therapy. We compared outcomes in infants receiving early caffeine therapy (initial dose before 3 days of life) and those receiving late caffeine therapy (initial dose at or after 3 days of life) through propensity scoring using baseline and early clinical variables. The primary outcome was the association between the timing of caffeine initiation and the incidence of bronchopulmonary dysplasia (BPD) or death. Results: We propensity score-matched 29 070 VLBW infants at a 1:1. Of infants receiving early caffeine therapy, 3681 (27.6%) died or developed BPD, compared with 4591 infants (34.0%) receiving late caffeine therapy (OR, 0.74; 99% CI, 0.69-0.80). Infants receiving early caffeine had a lower incidence of BPD (23.1% vs 30.7%; OR, 0.68; 95% CI, 0.63-0.73) and a higher incidence of death (4.5% vs 3.7%; OR, 1.23; 95% CI, 1.05-1.43). Infants receiving early caffeine therapy had less treatment of patent ductus arteriosus (OR, 0.60; 95% CI, 0.55-0.65) and a shorter duration of mechanical ventilation (mean difference, 6 days; P <.001). Conclusion: Early caffeine initiation is associated with a decreased incidence of BPD. Randomized trials are needed to determine the efficacy and safety of early caffeine prophylaxis in VLBW infants.

Copyright information:

© 2014 The Authors.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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