Caffeine not associated with irritable behaviour in very low-birth-weight infants
Introduction
Methylxanthines, such as caffeine (Caf) and aminophylline (Am), have been used for the treatment of apnea of prematurity (AOP) [1]. Methylxanthines are non-selective adenosine receptor antagonists. Adenosine is a neuromodulator that exerts a depressant effect on the central nervous system. Therefore, methylxanthines may enhance generalised central nervous excitation [2,3]. There is a concern that excessive excitement in the developing brain adversely affects neurobehavioural conditions [[3], [4], [5], [6]]. We have reported that Am was associated with neonatal irritable behaviour in preterm period [7]. Understanding the effects of drugs on neonatal behaviour is important for providing adequate individualized developmental care [8]. In an international randomized placebo-controlled trial, the caffeine for apnea of prematurity trial (CAP trial) clearly demonstrated the safety and efficacy of caffeine in treating premature infants [9,10]. Standard medication for AOP has changed from Am to Caf [11]. The effect of Caf on neonatal behaviour is more important clinically than that of Am. The present study investigated the effect of Caf on neonatal behaviour during the preterm period.
Section snippets
Subjects
Very low-birth-weight infants (VLBWI) cared for in the Oita University Hospital neonatal intensive care unit (NICU) from August 2012 to December 2018, and for whom parental written informed consent was obtained for video recording, were enrolled in this study. This study was a continuation of a previous study on the association between Am and behaviour [7]. Since the medication for AOP has changed from Am to Caf, the study period was determined so that the Caf group was equal in number to the
Participants
Within the study period, 72 VLBWI were admitted to our NICU. There were 4 deaths during the neonatal period and 1 case of chromosomal abnormality, which were excluded from the GMs assessment clinical research. Six cases did not give consent to participate in the clinical research. In addition, 4 cases that did not have GMs recording during 32 to 35 weeks of GA were excluded from this study. We also excluded cases with obvious central nervous system lesions: 3 cases with intraventricular
Discussion
This study was carried out with VLBWI without obvious brain anomalies or insults; therefore, this result of methylxanthine-associated irritable behaviour might reflect the physiological characteristics of an immature brain. The Am group frequently presented more tremulous movements at GA 32–33 weeks than the Caf and the NM group. The Caf group did not present differences from the NM group. These findings suggest that Caf, unlike Am, is not associated with irritable behaviour at a standard dose
Declaration of competing interest
All authors hereby declare that they have no financial or personal relationships with other people or organisations that could inappropriately influence (bias) this work.
Acknowledgements
This work was supported by JSPS KAKENHI Grant Number 15K11705 and 18K10748.
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