Intermittent Hypoxia and Caffeine in Infants Born Preterm (ICAF)

ICAF is funded by the National Institute of Child Health and Development (NICHD).

Caffeine treatment for apnea of prematurity and related intermittent hypoxia (IH) is almost universal, with treatment most commonly discontinued at 33-35 weeks post-menstrual age (PMA).   However, IH continues to occur in infants after routine discontinuation of caffeine, and persists after hospital discharge. Studies confirm that the IH occurring during spontaneous breathing after stopping routine caffeine is a manifestation of immature breathing control. It is unknown if this persistent IH results in acute injury, and in particular if extending the duration of caffeine treatment attenuates or prevents this acute injury.

This study will address three critical questions:

  1. Will extending caffeine treatment from 32-35 to 42 weeks PMA reduce extent of IH?
  2. Is persisting IH associated with biochemical, structural, or functional indicators of acute injury?
  3. Does caffeine treatment continued to 42 weeks PMA attenuate this acute injury?

To help answer these questions, we will enroll 220 preterm infants in this study from Neonatal Intensive Care Units (NICUs) in 8 hospitals in 6 metropolitan areas in the US. With the potential to identify early brain injury mediated by IH and mitigated by caffeine at appropriate dosing, as well as help inform optimum strategies for later definitive neurodevelopmental assessments based on nature of the acute brain injury, this study has potential to justify further neurodevelopmental outcome projects and contribute a significant public health benefit.