Objective: Caffeine therapy for treatment of apnea of prematurity has been well established over the past few years. Furthermore, recently some paper reported that the caffeine showed neuroprotective effect less than 28 weeks baby. On the other hand, there have been little reports about the optimal dose of caffeine in such as less than 28 weeks baby and no reports about the occurrence of toxic serum caffeine concentration. 

Aim: The aim of this study is to investigate if the preterm infants would show toxic serum caffeine concentration with recommended dose.

Method: We measured the serum caffeine concentration of thirteen preterm infants who admitted to Neonatal Intensive Care Unit of Shikoku Medical Center for Children and Adults and received caffeine therapy during a half-year period (2018 July to December).
Each infant was treated with a loading dose of caffeine citrate (20 mg/kg/day), followed by maintenance therapy (5 to 10 mg/kg/day) with one daily dose. We compared the serum caffeine concentration of 5mg/kg/day group with 10mg/kg/day group by using residual serum of daily blood test retrospectively.
The serum caffeine concentration was measured by high performance liquid chromatography.

Results: Of the 13 infants, 9 received 5 mg/kg/day (GA 29.3±1.2 wk, BW 1129±219 g) and 4 received 10 mg/kg/day dose(GA 25.6±1.6 wk, BW 791±123 g).
Of the 5mg/kg/day group, their serum caffeine concentration did not exceed the therapeutic level and never show toxic serum concentration.
However, of the 10mg/kg/day group, all of them exceeded the therapeutic level and 3 of them showed toxic serum concentration.

Conclusion: Of the recommended dose of caffeine, some preterm infants showed toxic serum caffeine concentration. It still be controversial about the optimal dose for less than 28 weeks baby, and we may need to monitor its serum concentration and adverse reaction.