Assistant Professor University of Texas Southwestern Medical School Dallas, Texas, United States
Background: Caffeine therapy reduces the incidence of bronchopulmonary dysplasia (BPD) in very-low-birth-weight (VLBW) infants (Schmidt, B et al CAP Trial; NEJM, 354, 2006) and improves survival without neurodevelopmental disability at 18–21 months (Schmidt, B. et al, NEJM, 357, 2007). Studies have shown that caffeine administration < 72 hours improve survival without BPD. However, there is a paucity of data on how early caffeine should be administrated after birth to demonstrate a reduction in BPD and/or mortality in Extremely Low Birth Weight (ELBW) infants. Objective: To evaluate the timing of caffeine administration and its effect on mortality and BPD in ELBW infants. Design/Methods: We conducted a retrospective chart review of all infants ≤ 28 weeks GA or birth weight ≤ 1000g admitted to a level 4 NICU from 1/1/2011 to 06/30/2022. A total of 537 ELBW infants were included in the analysis. The demographic profile of all infants is shown in the table (Fig.1). The timing of caffeine administration was classified into five groups: Caffeine ≤12h; Caffeine 12-24h; Caffeine 24-48h; Caffeine 48-72h and Caffeine >72h. Clinical outcomes studied included mortality, BPD, ROP, pulmonary hypertension (PH), IVH, NEC, and PDA (Fig.2). Chi-square test, ANOVA, and multiple logistic regression were used to analyze the results. Results: The caffeine groups were significantly related to an increase in the incidence of BPD/Mortality by univariate analysis, suggesting a delay in caffeine administration may be related to an adverse outcome of BPD/Mortality. On logistic regression, controlling for GA, caffeine ≤ 12h significantly reduces BPD/Mortality (p < 0.02) with a borderline significant reduction in caffeine ≤24h group (p < 0.051). BPD/Mortality risk increases by 1% for each hour delay in caffeine (p < 0.03), however, caffeine timing is no longer significant when GA is included in the model. The average time of caffeine administration was 4.73h and 7.81h in ≤ 12h and ≤ 24h, respectively.
Conclusion(s): The study results are interesting and suggest that caffeine administration closer to birth may have tangible benefits relating to clinical outcomes such as BPD and/or Mortality. We speculate that the caffeine effects may be directly related to the lungs and indirectly to a favorable alteration in hemodynamics by modulating the ductus. The study is limited by the retrospective nature, small sample size, and uneven distribution of infants at various GA. However, the direct relationship between caffeine timing and improved clinical outcomes needs a detailed prospective analysis. Slide1.jpeg
