Introduction
Apnea of prematurity (AOP) is defined as the abrupt cessation of breathing for at least 20 seconds in an infant with gestational age less than 37 weeks, followed by both bradycardia and oxygen desaturation[1]. AOP becomes more common with decreased birth weight, affecting 85% of neonates born weighing less than 1,500g[2]. For decades, Methylxanthines have been utilized to effectively treat apnea of prematurity. The preferred methylxanthine for this indication due to its broad therapeutic window and a prolonged serum half-life is caffeine citrate[3]. This finding has been validated in several independent experiments, leading to the widespread use of caffeine as the first-line AOP treatment[4].
Even though caffeine has been widely utilized in neonatal practice, there are no recognized and standardized caffeine administration protocols[5]. Concerns have been expressed about potential safety issues and adverse effects, some of which may be related to the use of caffeine prophylactically. Several studies have found that giving prophylactical caffeine to preterm infants at risk of apnea reduces the time they need for positive pressure ventilation[6]. Caffeine prophylaxis, in addition to its effect on reducing apnea of prematurity, has other benefits on infants multiple organ systems, that includes the brain, lungs, and cardiovascular systems, such as lowering the incidence of bronchopulmonary dysplasia and arterial catheter ligation. In contrast, there are findings suggest that taking caffeine prophylactically may increase the risk of overtreatment, including harms such as intracranial bleeding[7], plus research has found it may increase the mortality rate in premature during vulnerable periods[8].
Therefore, there is still controversy concerning whether the use of prophylactic caffeine improves clinical outcomes as compared to the strict use of caffeine as a therapeutic pharmacological agent. It is necessary to conduct definitive research to prove the comparative effects of prophylactic versus therapeutic caffeine. This meta-analysis aims to assess the effects of the prophylactic initiation of caffeine for apnea and related complications in very low birth weight infants to assist clinicians in continually optimizing their present practice.