Association between caffeine citrate exposure and necrotizing enterocolitis in preterm infants

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Purpose: The results of a case–control study of the potential role of caffeine citrate therapy in the development of necrotizing enterocolitis (NEC) are presented.

Methods: Patient records for a 10-year period were reviewed to collect sufficient data to test the hypothesis that newborns treated in a hospital’s perinatal intensive care unit for NEC might have had a higher cumulative exposure to caffeine citrate relative to that of neonates of similar postconceptional and postnatal age who did not develop NEC. Ninety-five cases of NEC were identified; each case was matched to a control case by gestational age and birth weight. To enable comparative analyses, each control was assigned an index date according to the number of days from birth to NEC diagnosis in the paired case. Data collected for analysis included patient demographics, information on caffeine citrate and concomitant medication use, and potential confounding factors.

Results: Analysis of aggregated data for the entire seven-day NEC event timeframe indicated no significant differences between cases and controls with regard to average caffeine citrate loading doses (p = 0.5), cumulative exposure (p = 0.2), and trough serum concentrations (p = 0.5); mean cumulative exposure values differed significantly at one time point (four days prior to NEC diagnosis (p = 0.04).

Conclusion: Cumulative exposure to caffeine citrate among infants who developed NEC and infants who did not develop NEC differed significantly at only one of six evaluated time points during the seven days before NEC development or the index date. There was no significant difference between groups in the proportions of patients who received caffeine citrate or in mean serum caffeine concentrations.


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