O impacto da utilização da terapia com cafeína no recém-nascido prematuro sobre a suscetibilidade a alterações na atividade cerebral : uma revisão sistemática

Abstract

Caffeine is a drug of choice for the treatment and prevention of apnea in newborn babies, thus reducing the pulmonary diseases, hypoxic births, and newborn mortality. The benefits appear to be related to the reversal of adenosine inhibitory effects on inspiration. Due to the neuromodulatory role of adenosine, particularly early in development, changes in neuromodulation are correlated with long-term changes related to susceptibility to seizure. Thus, it is common in the records of studies in neonatology or in the routine of neonatal intensive care units, an identification of clinical or electroencephalographic records related to brain activity. In fact, experimental studies using animals point to an increase in seizure sensitivity when caffeine exposure occurs during the neonatal phase. However, human studies appear to be less emphatic, although there is some surveillance on possible effects of caffeine over brain activity. Thus, the objective of this review is to systematically review the literature on the change in brain activity after exposure to caffeine for the treatment of apnea of prematurity. Comprehensive research was performed in the databases PUBMED, VHL, Web of Science and CINAHL. The PIC strategy was, Population: newborns to newborns < 37 weeks; Intervention: caffeine citrate therapy; Comparison: newborn infants < 37 weeks who did not receive caffeine citrate. The assessment of the quality of the studies was according to the Cochrane Rob 2 and Rob NewCastle-Ottawa Checklist. The protocol followed the guidelines from the System of Prospective Reviews and Preferred Meta-Analyses (PRISMA) and was registered in the International Registry of Systematic Reviews (PROSPERO - CRD420201277545). From the 3125 original studies, 23 were selected after applying the inclusion and exclusion criteria by independent reviewers. Fourteen of these studies were observational and nine were randomized controlled trials. The studies were variable in relation to the type of brain activity assessment and caffeine exposure protocols, making it impossible to carry out a metanalysis. The study of the primary outcome was performed as clinical register of seizure or by Electroencephalogram (EEG) register. Caffeine exposure varied across studies, with the most common regimen being 20 mg/kg loading dose, followed by 5-10 mg/kg/day maintenance dose. The seizure, at least clinically relevant, appears not to be a concern when the more common caffeine exposure protocol was used. Increasing in brain activity detected by EEG not associated to seizure, have being correlated to increased maturity of brain and should be better investigated for its possible impacts, whether positive or positive, in the long term.