A pilot randomized trial of high-dose caffeine therapy in preterm infants

BACKGROUND: Standard-dose caffeine improves white matter microstructural development assessed by diffusion MRI. We hypothesized that early high-dose caffeine would result in further improvement in white matter microstructural development. METHODS: Seventy-four preterm infants (≤30 weeks gestational age) were randomly assigned to either a high (80 mg/kg IV) or standard (20 mg/kg IV) loading dose of caffeine citrate in the first 24 hours of life. MRI and neurobehavioral testing were undertaken at term equivalent age. Infants returned at 2 years 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 two years of age did not differ between groups. CONCLUSIONS: 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.