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.