Caffeine versus theophylline for apnea of prematurity. Longterm effects of caffeine therapy for apnea of prematurity. Pdf comparison between caffeine and theophylline therapy. This study aimed to determine the effects of plasma caffeine levels based on standard dose and genetic variability on clinical response to caffeine citrate in. Apnoea of prematurity is common but infants should be assessed to exclude other causes of apnoea such as. Seventy neonates less than 33 weeks gestation, breathing spontaneously, were randomly assigned open. Methylxanthines have been the mainstay of pharmacological treatment of apnea of prematurity for more than 30 years. Caffeine therapy for apnea of prematurity n engl j med. Comparative efficacy and safety of caffeine and aminophylline. Caffeine for the treatment of apnea in bronchiolitis. Caffeine is a risk factor for osteopenia of prematurity in.
Aminophylline, theophylline, and caffeine have all been used to improve ventilation in neonates. However, little is known about the longterm effects of caffeine on sleep in the developing brain. Caffeine citrate therapy for apnea of prematurity request pdf. Consensusguidelinesformanagementofapneaofprematurity. The most frequent indication for therapy reported in cap was treatment of documented apnea, followed by the facilitation of the removal of an endotracheal tube. Reduction in developmental coordination disorder with. Caffeine is one of the most commonly utilized medications in the nicu. A pnea of prematurity aop is defined as the cessation of spontaneous breathing by a premature infant lasting for more than 20 seconds andor accompanied by hypoxia or bradycardia.
Apnoea of prematurity aop is one of the major challenges when treating preterm infants. Postoperative caffeine for preventing apnea in preterm infants. Caffeine has been widely used to treat apnea of prematurity for the past 30 years as well as to facilitate the extubation in very low birth weight infants. It is one of the most commonly administered drugs in nicus. Caffeine therapy for apnea of prematurity reduces the rates of cerebral palsy and cognitive delay at 18 months of age. Caffeine for preemies neonatology jama jama network. However, neonatal caffeine therapy results in significant intersubject variability. Neurobehavioral outcomes 11 years after neonatal caffeine. Neonatal caffeine therapy for apnea of prematurity reduces the rate of dcd at 5 years of age. The clinical data of 120 premature infants with apnea treated with oxygen therapy and either caffeine citrate 20 mgkgday.
Clinical pharmacology of caffeine citrate in preterm infants. Highlightscaffeine is widely used to treat apnea of prematurity aop in preterm infants. Infants were divided into 3 groups based on the initiation. Caffeine therapy for apnea of prematurity new england journal of. In infants 28 weeks gestation who do not require positive pressure support, one reasonable approach would be to await the occurrence of apnea before initiating therapy. Only about 20% of the neonatologists in the trial started caffeine for the prevention of apnea and the findings of cap cannot automatically be extrapolated to an exclusive prophylactic.
Timing of caffeine therapy and neonatal outcomes in preterm. Fiveyear followup from 2005 to 2011 in 31 of 35 academic hospitals. The evidence provided by those, however, is depressed by an information overload due to high heterogeneity in the characteristics as. High dose caffeine citrate for extubation of preterm infants. A retrospective cohort was used to compare the neonatal morbidity of 150 preterm neonates with gestational age. Caffeine is a common treatment for neonatal intensive care management of the developmental complication of apnea of prematurity in preterm infants. Pdf apnea of prematurity aop affects the majority of infants born prematurely. Apnoea in premature infants and caffeine therapy infant journal. Caffeine treatment for apnea of prematurity and the. Apnea of prematurity american academy of pediatrics. The optimal time to start caffeine therapy in infants at risk of apnea is not known.
The purpose of this study was to compare the therapeutic effect and side effects of caffeine and aminophylline in the treatment of idiopathic apnea of prematurity. These authors observed that prophylactic use of methylxanthine therapy for apnea of prematurity can possibly be attributed to the beneficial effects of caffeine. Efficacy of caffeine in treatment of apnea in the lowbirthweight infant. Survival without disability to age 5 years after neonatal caffeine therapy for apnea of prematurity. Caffeine and theophylline for apnea of prematurity examined. Caffeine for the treatment of apnea in the neonatal intensive. Oct 01, 2016 administration of a higher dose of caffeine than what we used in the present study has been described previously.
The caffeine therapy for apnea of prematurity cap trial has shown that. Caffeine therapy practice in the management of apnea of. Nov 12, 2020 apnoea of prematurity aop is among the most common diagnoses in the neonatal intensive care unit. Caffeine for apnea of prematurity cap full text view. Caffeine therapy for apnea of prematurity reduces the rate of bronchopulmonary dysplasia in infants with very low birth weight.
Apnea of prematurity is a common condition that is usually treated with caffeine, an adenosine receptor blocker that has powerful influences on the central nervous system. The effects of caffeine on heart rate variability in. Objective to determine whether neonatal caffeine therapy has lasting benefits or newly apparent risks at early school age. The cumulative dose and duration of therapy of caffeine, as well as steroid are associated with osteopenia of prematurity in this cohort. Infants were divided into 3 groups based on the initiation timing of. Future studies are needed to confirm these findings and determine the lowest dose of caffeine needed to treat effectively apnea of prematurity. Clinical pharmacology of caffeine citrate in preterm infants scielo.
Caffeine citrate is it a silver bullet in neonatology. Efficacy and safety of different maintenance doses of. Tertiarycare referral centre and a teaching institution in southern india. The effects of caffeine on heart rate variability in newborns. Neonatal caffeine therapy for apnea of prematurity improved visuomotor, visuoperceptual, and visuospatial abilities at age 11 years. The pharmacokinetic profile of caffeine was studied in 32 premature newborn infants with apnea. Module wb2108 objectives neonatal drugscardiotonics. We evaluated the shortterm outcomes before the first discharge home. In preterm infants, shortterm and longterm pulmonary and neurodevelopmental benefits of therapy are well documented in the literature. Although caffeine therapy has a benefit on gross motor skills in schoolaged children, effects on. The chart showing pdf series, word series, html series, scan qr codes.
We randomly assigned 2006 infants with birth weights of 500 to 1250 g during the first 10 days of life to receive either caffeine or placebo, until drug therapy for apnea of prematurity was no longer needed. Pdf methylxanthines reduce the frequency of apnea of prematurity and the need for mechanical ventilation during the first seven days of. Apnoea is one of the most common clinical manifestations in preterm infants. The aim was to confirm the efficacy of caffeine citrate in the treatment of recurrent intermittent hypoxia and bradycardia in preterm newborns with. In addition to improved health outcomes, caffeine treatment is seen to. Pdf caffeine therapy for apnea of prematurity arne. Caffeine, a methylxanthine, is the preferred agent to treat or prevent apnea of prematurity. Trial was conducted from february 2012 to january 2015. Design, setting, and participants fiveyear followup. Caffeine therapy for apnea of prematurity improves the rate of survival without neurodevelopmental disability at 18 to 21 months in infants with very low birth weight.
Caffeine citrate for the treatment of apnea of prematurity. Steer p, flenady v, shearman a, charles b, gray p, hendersonsmart d, et al. Caffeine is widely used for the treatment of neonatal apnea, but there is no agreement on the optimum maintenance dose for preterm infants. The aim was to confirm the efficacy of caffeine citrate in the treatment of recurrent intermittent hypoxia and bradycardia in preterm newborns with primary apnea.
Frontiers caffeine citrate for apnea of prematurity. Newborn critical care center nccc clinical guidelines. This study aimed to evaluate the therapeutic effect of caffeine citrate on early premature infants with apnea of prematurity aop, and the impact on movement. Caffeine is widely used to treat apnea of prematurity. Effect of caffeine and aminophylline on apnea of prematurity. The rate of dcd was lower in those treated with caffeine 11. Guideline for caffeine use in preterm infants south west neonatal. The aims of this metaanalysis were to compare the efficacy and safety of high versus low maintenance doses of caffeine citrate for the treatment of apnea in premature infants. The dosage used in the largest randomised controlled trial rct conducted to date investigating caffeine in preterm infants, the caffeine for apnea of prematurity cap trial, is the most often quoted template for local caffeine therapy protocols. Apnea of prematurity aop commonly occurs in preterm infants and is. Caffeine citrate has been approved in china for the management of apnea of prematurity. Caffeine versus aminophylline in combination with oxygen. With respect to adverse effects of drug therapy, feeding diffi culties such as residual volume, abdominal distension. Methylxanthine drugs such as caffeine are used to prevent or treat periodic breathing and breathholding spells in premature infants.
Schmidt b, roberts rs, davis p, doyle lw, barrington kj, ohlsson a, et al. Early caffeine administration and neurodevelopmental outcomes. It is the first choice among all methylxanthines because of its efficacy, better tolerability and wider therapeutic index as well as longer halflife. Over the last two decades, caffeine has gained popularity due to its wider therapeutic window and better safety. In the pioneering study caffeine for apnea of prematurity cap trial, infants who. Design, setting, and participants fiveyear followup from 2005 to 2011 in 31. Here, we evaluated the efficacy of early caffeine 12 dol in decreasing the incidence of adverse neonatal outcomes. Caffeine for the treatment of apnea in the neonatal. Caffeine citrate is considered preferable because it is better tolerated and has fewer side effects, a larger margin of safety, a higher therapeutic index, and a longer halflife.
However, most studies suggest that caffeine is detrimental to the developing brain. Methods we randomly assigned 2006 infants with birth weights of 500 to 1250 g to receive either caffeine or placebo until therapy for apnea of prematurity was no. To determine whether neonatal caffeine therapy has lasting benefits or newly apparent risks at early school age. Apnea of prematurity is one of the most common reasons for the initiation of drug therapy in neonatal medicine. While robust evidence supports the use of standard doses of caffeine for apnea of prematurit. It is uncertain whether methylxanthines have longterm effects on neurodevelopment and growth. Timing of caffeine therapy and neonatal outcomes in. Thephophylline, aminophylline, and caffeine citrate have demonstrated effectiveness in the treatment of apnea of prematurity. Caffeine therapy for apnea of prematurity introduction apnea in the premature infant can be caused by decreased central respiratory drive, inability to maintain airway patency, and other causes. The results indicated that a population proportion with recurrent episodes of apnea following withdrawal of drug therapy reached to 11 and 14% in the caffeine and aminophyllinetreated infants, respectively, indicating that the efficacy of caffeine was superior to that of aminophylline in treating the apnea of prematurity, under the three. Comparison between caffeine and theophylline therapy for. Survival without disability to age 5 years after neonatal. We randomly assigned 2006 infants with birth weights of 500 to 1250 g during the first 10 days of life to receive either caffeine or placebo, until drug therapy for apnea of prematurity was no. Both prevention and treatment of apnea of prematurity are considered the main indication for.
The caffeine for apnea of prematurity cap trial randomized 2,006 preterm infants to neonatal caffeine therapy or placebo and showed beneficial results, with caffeine resulting in lower rates of bronchopulmonary dysplasia and severe retinopathy of prematurity before discharge, and reduced risks of cerebral palsy and cognitive delay at 18. Caffeine treatment for apnea of prematurity and the influence. Pdf caffeine therapy for apnea of prematurity researchgate. The number of apnea events per day according to each time period such as before treatment, 1 to 3 days, 4 to 7 days, and 8 to 14 days after treatment were assessed. Overall neonatal caffeine therapy, at the doses used in the cap trial, appe. This clinical trial was conducted as a condition of regulatory approval. The maximal dose of caffeine that is safe to use for aop needs to be determined. Background methylxanthine therapy is commonly used for apnea of prematurity but in the absence of adequate data on its efficacy and safety. To compare standard doses of theophylline and caffeine for apnea of prematurity in terms of apnea frequency and assess the need for therapeutic drug monitoring.
General intelligence, attention, and behavior were not adversely affected by caffeine, which highlights the longterm safety of caffeine therapy for apnea of prematurity in very low birth weight neonates. To compare the efficacy and safety of standard doses of caffeine and aminophylline for apnea of prematurity. The pdf version of this handbook uses bookmarks to flag the start of each. However, despite its frequent use in routine neonatal practice, there are currently no commonly. Caffeine is effective in the treatment of apnea of prematurity. Jan 17, 2012 to evaluate the efficacy and safety of caffeine citrate for treatment of apnea of prematurity. The present study was conducted to investigate the clinical significance of caffeine and aminophylline in the treatment of premature infants with apnea under varying conditions of oxygen o 2 delivery. Caffeine can have beneficial or adverse effects on the developing brain. Decreased need for supplemental oxygen at a postmenstrual age of 36 weeks shourter duration of respiratory support.
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