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

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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.

Section snippets

Methods

We used a large, multicenter dataset from the Pediatrix Medical Group.16 The use of this dataset has been described previously.1 Infants discharged between 1997 and 2010 were eligible for evaluation of primary and secondary outcomes if they met the following inclusion criteria: (1) receipt of caffeine during the course of hospitalization; (2) VLBW (<1500 g birth weight); and (3) admission within 1 day of birth. Exclusion criteria included treatment with multiple methylxanthines and early

Results

Of the 54 707 infants meeting the study's inclusion criteria, 29 070 (53%) were PS-matched at 1:1 (Figure 1). PS-matched infants in the early and late caffeine groups had similar baseline characteristics, with no significant differences in any of the matched variables, including mean birth weight (1055 g vs 1054 g; P = .77) and GA (28.1 weeks vs 28.0 weeks; P = .70) (Table I).

Discussion

In VLBW infants, early caffeine initiation was associated with reduced neonatal morbidity, including a decreased incidence of BPD and of PDA requiring treatment. In addition, the centers in this study have shifted toward earlier initiation of caffeine therapy over time, with a majority of VLBW infants receiving early caffeine therapy in 2010. Although the observational study design limits our ability to draw inferences regarding causality, the effect of early caffeine therapy on improving

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    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 (HHSN267200700051C, HHSN275201000003I, and 1K23HL092225-01), 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). The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Army, Department of Defense, US government, or NIH. The authors declare no conflicts of interest.

    Contributed equally.

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