Efficacy of aminophylline vs. caffeine for preventing apnea of prematurity

Abstract

Background Apnea of prematurity (AOP) usually occurs in neonates with a gestational age < 34 weeks. The World Health Organization has recommended the administration of caffeine or aminophylline to prevent AOP, but the efficacy of aminophylline remains unclear, and caffeine citrate is not available in Indonesia. Objective To compare the efficacy of aminophylline to that of caffeine for preventing AOP. Methods This single-blind, clinical trial was conducted on neonates (gestational age 28-34 weeks) who were able to breathe spontaneously within the first 24 hours of life and admitted to Sanglah Hospital from December 2012 to April 2013. Subjects were randomly allocated into two groups, namely groups of aminophyllin and caffeine. The aminophylline group received aminophylline dihydrate at an initial dose of 10 mg/kg body weight, then continued with a maintenance dose of 2.5 mg/kg body weight every 12 hours. The caffeine group received anhydrous caffeine at an initial dose of 10 mg/kg body weight, then continued with a maintenance dose of 1.25 mg/kg body weight every 12 hours. We followed subjects up until they were 10 days old. Subjects received per oral therapy for seven days. The efficacy comparison between the two groups was assessed by Chi-square test with 95% confidence interval (CI) and a statistical significance value of P < 0.05. We used multivariate test to analyze the confounding factors. Results Ninety-six subjects participated in this study; 48 subjects received aminophylline therapy and the other 48 subjects received caffeine therapy. Twenty-eight subjects experienced apnea: 13 subjects from the aminophylline group (27.1%), and 15 subjects from the caffeine group (31.3%). It appeared that aminophylline was slightly better compared to caffeine, but the difference was not statistically significant, with a relative risk of 0.9 (95% CI 0.5 to 1.3; P=0.8). We found vomiting to be a side effect of both therapies, and not significantly different between groups. Sepsis From the Department of Child Health, Udayana University Medical School/Sanglah Hospital, Denpasar1 and Gadjah Mada University Medical School/Sardjito Hospital, Yogyakarta2. Reprint requests to: Hendy, Department of Child Health, Udayana University Medical School, Sanglah Hospital, Jl. Pulau Nias, Denpasar, Bali 80114. Tel./Fax: [phone]. E-mail: hendyhalim.md@gmail. com. Infant prematurity is defined as a gestational age of < 37 weeks. Africa has the highest birth rate of premature infants of 11.9%, while that of Southeast Asia is approximately 11.1%.1 The main issue that premature infants face is apnea. Apnea is caused by incomplete development of the respiratory center, and is known as apnea of prematurity (AOP). Several factors underlie the necessity of AOP prevention: an 85% incidence of AOP in infants with gestational age <34 weeks,2 difficulty in diagnosing AOP, unpredictable onset, short- and long-term effects, long treatment length and requirement of intensive care. The World Health and hyaline membrane disease were found to be confounding factors in this study. Conclusion Aminophylline and caffeine have similar efficacy with regards to preventing AOP.

Keywords

• prevent, apnea of prematurity, aminophylline, caffeine