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A pilot randomized trial of high-dose caffeine therapy in preterm infants
Christopher McPherson1, Jeffrey J Neil2, Tiong Han Tjoeng3
11] Department of Pharmacy, Brigham and Women's Hospital, Boston, Massachusetts [2] Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Background:
Standard-dose caffeine improves white matter microstructural development assessed by diffusion magnetic resonance imaging (MRI). We hypothesized that early high-dose caffeine would result in further improvement in white matter microstructural development.
Methods:
Seventy-four preterm infants (≤30 wk gestational age) were randomly assigned to either a high (80 mg/kg i.v.) or standard (20 mg/kg i.v.) loading dose of caffeine citrate in the first 24 h of life. MRI and neurobehavioral testing were undertaken at term equivalent age. Infants returned at 2 y of age for developmental testing.
Results:
Clinical characteristics were similar between groups, with the exception of higher maternal age in the high-dose caffeine group. There was an increased incidence of cerebellar hemorrhage in infants randomized to high-dose caffeine (36 vs. 10%, P = 0.03). Infants in the high-dose caffeine group also demonstrated more hypertonicity (P = 0.02) and more deviant neurologic signs (P = 0.04) at term equivalent age. Diffusion measures at term equivalent age and developmental outcomes at 2 y of age did not differ between groups.
Conclusion:
Preterm infants randomized to early high-dose caffeine had a higher incidence of cerebellar injury with subsequent alterations in early motor performance. The results of this pilot trial discourage a larger randomized controlled trial.
