Amer J Perinatol 2015; 32(09): 879-886
DOI: 10.1055/s-0034-1543981
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A Pilot Randomized Controlled Trial of Early versus Routine Caffeine in Extremely Premature Infants

Anup C. Katheria1, Jason B. Sauberan1, Devang Akotia1, Wade Rich1, Jayson Durham1, Neil N. Finer1, 2
  • 1Neonatal Research Institute, Sharp Mary Birch Hospital for Women and Newborns, San Diego, California
  • 2Department of Pediatrics, University of California, San Diego, California
Further Information

Publication History

27 October 2014

05 December 2014

Publication Date:
21 January 2015 (eFirst)


Objective This study aims to compare the effects of early and late (routine) initiation of caffeine in nonintubated preterm neonates.

Study Design A total of 21 neonates < 29 weeks gestational age were randomized to receive intravenous caffeine citrate (20 mg/kg) or placebo either before 2 hours of age (early) or at 12 hours of age (routine). This was an observational trial to determine the power needed to reduce the need for endotracheal intubation by 12 hours of age. Other outcomes included comparisons of cerebral oxygenation, systemic and pulmonary blood flow, hemodynamics, hypotension treatment, oxygen requirement, and head ultrasound findings.

Results There was no difference in the need for intubation (p = 0.08), or vasopressors (p = 0.21) by 12 hours of age. Early caffeine was associated with improved blood pressure (p = 0.03) and systemic blood flow (superior vena cava flow, p = 0.04 and right ventricular output, p = 0.03). Heart rate, left ventricular output, and stroke volume were not significantly affected. Cerebral oxygenation transiently decreased 1 hour after caffeine administration. There were no differences in other outcomes.

Conclusion This pilot study demonstrated the feasibility of conducting such a trial in extremely preterm neonates. We found that early caffeine administration was associated with improved hemodynamics. Larger studies are needed to determine whether early caffeine reduces intubation, intraventricular hemorrhage, and related long-term outcomes.