Aminophylline Therapy and the Neurodevelopment in Premature Infants

Abstract

We read with interest the article by Tey et al, 1 describing the correlation between aminophylline therapy and neurological outcome in very low birth weight (VLBW) infants. They speculated that aminophylline therapy for apnea of prematurity (AOP) had no apparent and additional risk on the neurodevelopmental outcomes of VLBW infants at a corrected age of 18 months. In total, 104 infants (birth body weight < 1500 g) were deemed eligible to participate in this study. Aminophylline was used in 52 of these infants for the treatment of AOP. Fifty-two gestational age-matched infants with AOP who did not receive aminophylline were selected as the controls. The rate of bronchopulmonary dysplasia (BPD) was significantly higher in the aminophylline group (48.08% vs. 21.15%, unadjusted odds ratio: 3.45, p < 0.005). There was a tendency to show that the aminophylline group had fewer patients with scores on both the psychomotor developmental index (PDI) and mental developmental index (MDI) < 70 than the control group at a corrected age of 12 months (7.69% in the aminophylline group vs. 13.46% in the control group, p Z 0.34) and at a corrected age of 18 months (3.85% in the aminophylline group vs. 11.54% in the control group, p Z 0.14). However, these differences were not statistically significant. This result suggests that aminophylline did not adversely affect the neurodevelopment of VLBW preterm infants at a corrected age of 6e18 months. Caffeine is a more effective methylxanthine for the treatment of AOP. 2 However, intravenous aminophylline is widely used in NICUs for the treatment of AOP in Taiwan due to the lack of intravenous caffeine. 1 We expected the results of the study to indicate that aminophylline did not adversely affect the neurodevelopment of VLBW preterm infants at a corrected age of 6e18 months. However, we have some concerns with the results. The authors stated that there were few clinical reports on the efficacy of aminophylline for BPD prevention or treatment. In fact, Armanian et al 3 published one paper on a similar topic since 2014. The rate of BPD was significantly higher in the aminophylline group in this study. This is in contrast with that in the study of Armanian et al. 3 Armanian et al found that infants who received aminophylline therapy had clearly shorter oxygen dependency times than the infants in the control group. The incidence of BPD was significantly different between the two groups. Only two infants (8.7%) who received aminophylline therapy developed BPD, when compared to 11 infants (44.0%) who did not receive aminophylline (p Z 0.006). Tey et al 1 speculated that the high percentage of BPD in the aminophylline group was because these infants had more severe and longer AOP, and consequently they needed longer nasal continuous positive airway pressure (NCAP) support combined with aminophylline treatment to prevent hypoxic insult to the brain. Since the disease severity of AOP and the incidence of BPD were different in these two groups, the authors should exclude the influence of these two confounding factors on neurological outcome in VLBW infants receiving aminophylline therapy. Then, the conclusion that aminophylline did not adversely affect the neurodevelopment of VLBW preterm infants at a corrected age of 6e18 months will be more convincing. Although aminophylline therapy for AOP is widely used in Taiwan, its safety concerning neurological outcome in VLBW infants remains an issue. Further long-term follow-up and a prospective randomized clinical trial are necessary.