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: +62-361-244038. 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.