CLINICAL INVESTIGATION Relationship of Caffeine Dosing With Serum Alkaline Phosphatase Levels in Extremely Low-Birth-Weight Infants

OBJECTIVE To determine whether patients receiving higher doses of caffeine have increased alkaline phosphatase (ALP) levels, as a biomarker for osteopenia. METHODS This descriptive, retrospective study included 152 extremely low-birth-weight infants (ie, ,1 kg) admitted from January 1, 2007, to September 30, 2009, who received caffeine for .2 weeks. Patients were divided into a low-dose (,7.5 mg/kg/day) and high-dose (� 7.5 mg/kg/day) group based on maximum caffeine dose received. The primary objective was to compare peak ALP levels between groups. Secondary objectives included a comparison of caffeine regimens and risk factors for osteopenia between groups and identification of factors significantly related to increase in ALP. Between-group analysis was performed using the chi-squared or Fisher exact test and Wilcoxon Mann-Whitney median test or t-tests where appropriate. A linear regression model was used, with peak ALP as the dependent variable. RESULTS A majority of the patients (n¼122) were included in the high-dose caffeine group. No significant difference in maximum ALP level between groups (median, 599.5, versus 602.5 units/L, p¼0.72). Gestational age and birth weight were inversely related to ALP, whereas parenteral nutrition duration was directly related. No significant relationship between caffeine dose and ALP was identified. CONCLUSIONS In this preliminary study, using ALP as a biochemical marker for bone turnover, there does not appear to be a dose-related effect between ALP and caffeine dose.