The association of salivary caffeine levels with serum concentrations in premature infants with apnea of prematurity

The purpose of this paper is to verify whether the concentrations of caffeine in saliva are comparable to serum concentrations in preterm infants who are treated with caffeine for apnea of prematurity. This is a prospective observational study. Eligible participants were newborn infants < 37 weeks of gestational age treated with oral or intravenous caffeine for apnea of prematurity. Two paired samples of saliva and blood were collected per patient. Tube solid-phase microextraction coupled online to capillary liquid chromatography with diode array detection was used for analysis. A total of 47 infants with a median gestational age of 28 [26–30] weeks and a mean of 1.11 ± 0.4 kg of birth weight. Median postmenstrual age, when samples were collected, was 31 [29–33] weeks. Serum caffeine median levels of 19.30 μg/mL [1.9–53.90] and salivary caffeine median levels of 16.36 μg/mL [2.20–56.90] were obtained. There was a strong positive Pearson’s correlation between the two variables r = 0.83 ( p < 0.001). Conclusion : The measurement of salivary caffeine concentrations after intravenous or oral administration offers an alternative to serum caffeine monitoring in apnea of prematurity. Measurement of salivary concentration minimizes blood draws, improves blood conservation, and subsequently minimizes painful procedures in premature infants. What is Known: • Salivary sampling may be useful when is applied to extremely low birth weight infant, in whom blood sampling must be severely restricted. What is New: • The measurement of caffeine salivary concentrations after intravenous or oral administration offers an alternative to serum caffeine monitoring in apnoea of prematurity. • Salivary sampling may be a valid non-invasive alternative that could be used to individualize and optimize caffeine dose.