Trends in caffeine use and association between clinical outcomes and timing of therapy in very low birth weight infants.
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.


METHODS
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).


CONCLUSIONS
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.
Department of Pediatrics, Uniformed Services University of Health Sciences, Bethesda, MD.
Nicole R
NR
Dobson
Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA.
Ravi M
RM
Patel
Duke Clinical Research Institute, Durham, NC.
P Brian
PB
Smith
Womack Army Medical Center, Fort Bragg, NC.
Devon R
DR
Kuehn
University of North Carolina School of Public Health, Chapel Hill, NC.
Jennifer
J
Clark
Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA.
Shilpa
S
Vyas-Read
University of North Carolina School of Public Health, Chapel Hill, NC.
Amy
A
Herring
Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Matthew M
MM
Laughon
Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA.
David
D
Carlton
Department of Pediatrics, Uniformed Services University of Health Sciences, Bethesda, MD.
Carl E
CE
Hunt
D001997:Bronchopulmonary Dysplasia / Q000453:epidemiology / Q000517:prevention & control* / Q000628:therapy; D002110:Caffeine / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004374:Ductus Arteriosus, Patent / Q000628:therapy; D005260:Female; D006801:Humans; D015994:Incidence; D007226:Infant Mortality; D007231:Infant, Newborn; D007234:Infant, Premature; D019102:Infant, Very Low Birth Weight; D015931:Intensive Care, Neonatal / Q000379:methods / Q000706:statistics & numerical data / Q000639:trends*; D008297:Male; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data / Q000639:trends*; D057216:Propensity Score; D012121:Respiration, Artificial / Q000706:statistics & numerical data; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
D000697:Central Nervous System Stimulants; D002110:Caffeine