Serum caffeine concentrations and short-term outcomes in premature infants of ⩽29 weeks of gestation

J Perinatol. 2015 Jun;35(6):434-8. doi: 10.1038/jp.2014.226. Epub 2014 Dec 18.


Objective: Caffeine is effective in the treatment of apnea of prematurity but it is not well known if the therapeutic concentration of the drug has an impact on other neonatal outcomes such as chronic lung disease (CLD). The aim of this study was to determine if there is an association between caffeine concentrations and the incidence of CLD in premature infants of ⩽29 weeks of gestation.

Study design: A retrospective chart review of all the infants born ⩽29 weeks of gestation from 2007 to 2011, who survived until discharge or 36 weeks postmenstrual age, was conducted. Caffeine concentrations were obtained weekly on infants getting the drug. Average caffeine concentrations (ACCs) were determined for the duration of caffeine therapy and correlated with CLD, length of stay (LOS), oxygen at discharge (OD), duration of ventilation (DV) and total charges for hospitalization for each patient.

Results: Of the 222 eligible infants, 198 met the inclusion criteria. ACC for infants without CLD was 17.0±3.8 μg ml(-1) compared with infants with CLD 14.3±6.1 μg ml(-1) (P<0.001). Infants receiving high ACC (>14.5 μg ml(-1)) had lower incidence of patent ductus arteriosus, lesser number of days on ventilator and oxygen, lesser need for diuretics, lower incidence of CLD, were more likely to go home without supplemental OD and had lower LOS and lower total hospital charges (all differences were significant P<0.05) Multiple logistic regression modeling after adjusting for confounding variables indicated that higher caffeine concentrations were significantly associated with decrease in CLD. Receiver operating curve analysis confirmed a significant predictive ability of caffeine concentration for CLD with a cutoff concentration of 14.5 μg ml(-1) (sensitivity of 42.6 and specificity of 86.8). The AUC (area under the curve) for the prediction of CLD was 0.632 (95% confidence interval 0.56-0.69, P=0.009).

Conclusions: Caffeine concentrations >14.5 μg ml(-1) were strongly correlated with reduced CLD in infants born at ⩽29 weeks of gestation. Higher caffeine concentrations were associated with decreased total hospital charges, DV, OD and LOS. Additional randomized trials are needed to confirm these findings, to identify ideal serum concentrations and determine possible long-term neurologic benefits.

MeSH terms

  • Caffeine / blood*
  • Chronic Disease
  • Gestational Age
  • Hospital Charges
  • Humans
  • Infant, Premature / blood*
  • Length of Stay
  • Lung Diseases / epidemiology*
  • Lung Diseases / prevention & control
  • Lung Injury
  • ROC Curve
  • Retrospective Studies
  • Sensitivity and Specificity


  • Caffeine