Efeitos do tratamento com cafeína para a apneia da prematuridade sobre o sono : uma revisão sistemática da literatura

Abstract

Apnea of prematurity can lead to death or leave sequelae that affect quality of life. Treatment and prophylaxis have been carried out for decades with caffeine citrate as the first choice, with proven efficacy and safety, both for the treatment of apnea of prematurity and for reducing the incidence of bronchopulmonary dysplasia, patent ductus arteriosus, retinopathy of prematurity and survival without neurodevelopmental disabilities. Caffeine is a non-specific antagonist of adenosine P1 receptors. Among the functions of adenosine is that of being a neuromodulator of vital functions, such as sleep, and, however, there is no consensus on the effects of this treatment on sleep, especially when considering the important role of adenosine in the early development of the brain for sleep maturation. We performed a systematic literature search in PubMed, Web of Science, and Virtual Health Library to identify studies investigating the short- and long-term effects of caffeine used for apnea of prematurity and sleep parameters. For a comprehensive evaluation, we used the PIC strategy, with the Population being preterm infants, caffeine citrate being the Intervention and preterm infants without exposure to caffeine being the Comparison. Two independent reviewers applied inclusion and exclusion criteria, assessed risk of bias, extracted, and analyzed data. The PROSPERO registration number is CRD42021282536. Of 4019 studies, 20 were considered eligible, including randomized clinical trials and follow-ups, and observational studies. The analyzed sleep parameters, evaluation phase and tools to evaluate sleep were very variable. Main findings can be summarized as: (i) the most common caffeine treatment protocol for apnea did not affect the main sleep parameters; and (II) there is some evidence that caffeine when administered earlier, in higher doses or for longer periods, especially in very premature newborns, may affect sleep parameters. The search for better results from caffeine treatment for very premature babies has been done through changes in caffeine concentration and exposure time protocols, which have not yet evaluated short- and long-term effects, including sleep maturation.