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      Prophylactic Aminophylline for Prevention of Apnea at Higher-Risk Preterm Neonates

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          Abstract

          Background:

          A few studies have been carried on preventive drugs for apnea of preterm neonates.

          Objectives:

          This study aimed to assess the safety and prophylactic effects of aminophylline on the incidence of apnea in premature neonates.

          Patients and Methods:

          This study was a randomized clinical trial (RCT) research. The prophylactic effect of aminophylline on apnea was investigated in premature babies in our NICU (IRAN-Isfahan). In the study group (A), 5 mg/kg aminophylline was initially administered as a loading dose. Then, every 8 hours, 1.5 mg/kg was given as maintenance dose for the next 10 days. In the control group (C), no aminophylline was used during the first ten days of life.

          Results:

          Fifty-two neonates were randomized for the study and all of them completed it. Primary outcomes were clearly different between the two groups. Only 2 infants (7.7%) who had been placed in aminophylline group developed apnea, as compared to 16 infants (61.5%) in the control group (P < 0.001). Three and four neonates (11.5%, 15.4%) in the aminophylline group developed bradycardia and cyanosis respectively, as compared to 16 infants (61.5%) who did not receive aminophylline (P < 0.001). Median time of need to NCPAP (Nasal Continuous Positive Airway Pressure) was 1 (0 - 4) days and 2.5 (0.5 - 6.5) days in group A and C, respectively (P = 0.03). No side effects were reported in neonates (P > 0.999). Median time of hospitalization was shorter in aminophylline group (P = 0.04).

          Conclusions:

          This study supports the preventative effects of aminophylline on apnea in extreme premature infants. In other words, the more premature an infant, the greater the preventative effect of aminophylline on the incidence of apnea and bradycardia.

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          Most cited references20

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          Caffeine therapy for apnea of prematurity.

          Methylxanthines reduce the frequency of apnea of prematurity and the need for mechanical ventilation during the first seven days of therapy. It is uncertain whether methylxanthines have other short- and long-term benefits or risks in infants with very low birth weight. 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. We evaluated the short-term outcomes before the first discharge home. Of 963 infants who were assigned to caffeine and who remained alive at a postmenstrual age of 36 weeks, 350 (36 percent) received supplemental oxygen, as did 447 of the 954 infants (47 percent) assigned to placebo (adjusted odds ratio, 0.63; 95 percent confidence interval, 0.52 to 0.76; P<0.001). Positive airway pressure was discontinued one week earlier in the infants assigned to caffeine (median postmenstrual age, 31.0 weeks; interquartile range, 29.4 to 33.0) than in the infants in the placebo group (median postmenstrual age, 32.0 weeks; interquartile range, 30.3 to 34.0; P<0.001). Caffeine reduced weight gain temporarily. The mean difference in weight gain between the group receiving caffeine and the group receiving placebo was greatest after two weeks (mean difference, -23 g; 95 percent confidence interval, -32 to -13; P<0.001). The rates of death, ultrasonographic signs of brain injury, and necrotizing enterocolitis did not differ significantly between the two groups. Caffeine therapy for apnea of prematurity reduces the rate of bronchopulmonary dysplasia in infants with very low birth weight. (ClinicalTrials.gov number, NCT00182312.). Copyright 2006 Massachusetts Medical Society.
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            • Article: not found

            Apnea, sudden infant death syndrome, and home monitoring.

            (2003)
            More than 25 years have elapsed since continuous cardiorespiratory monitoring at home was suggested to decrease the risk of sudden infant death syndrome (SIDS). In the ensuing interval, multiple studies have been unable to establish the alleged efficacy of its use. In this statement, the most recent research information concerning extreme limits for a prolonged course of apnea of prematurity is reviewed. Recommendations regarding the appropriate use of home cardiorespiratory monitoring after hospital discharge emphasize limiting use to specific clinical indications for a predetermined period, using only monitors equipped with an event recorder, and counseling parents that monitor use does not prevent sudden, unexpected death in all circumstances. The continued implementation of proven SIDS prevention measures is encouraged.
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              Summary proceedings from the apnea-of-prematurity group.

              Apnea of prematurity (AOP) is found in >50% of premature infants and is almost universal in infants who are 20 seconds or for >10 seconds if associated with bradycardia or oxygen desaturation), but there is no consensus about the duration of apnea, the degree of change in oxygen saturation, or severity of bradycardia that should be considered pathologic. Although caregivers are able to respond successfully to apnea events with drugs (as well as physical and mechanical interventions) in the NICU, it remains unproven whether such interventions have any long-term effects. One of the most effective drugs, caffeine citrate, is currently labeled for short-term use only and within a limited gestational-age population. Clinicians often use off-label drugs that have been approved for gastroesophageal reflux disease, which is common in premature infants, with the belief that such treatments also have an impact on AOP, although this link has never been demonstrated. Key treatment issues include (1) lack of standardization for definition, diagnosis, and treatment of AOP, (2) unproven benefit of intervention, (3) lack of real-time data documenting AOP events, (4) unevaluated sustained treatment improvement at 7 days or later, (5) failure to address confounding conditions, (6) unsubstantiated AOP-gastroesophageal reflux disease relationship, and (7) undetermined role of AOP affecting long-term neurodevelopmental outcomes. In addressing study-design issues, the pulmonary group identified (1) key questions about neonatal apnea, (2) methodologic requirements for study, (3) appropriate outcome measures, and (4) ethical considerations for future studies. This article describes a sample framework for the study of apnea in neonates and identifies future research needs. Plenary-session discussion points are also listed.
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                Author and article information

                Journal
                Iran Red Crescent Med J
                Iran Red Crescent Med J
                10.5812/ircmj
                Kowsar
                Iranian Red Crescent Medical Journal
                Kowsar
                2074-1804
                2074-1812
                05 August 2014
                August 2014
                : 16
                : 8
                : e12559
                Affiliations
                [1 ]Department of Pediatrics, Child Growth and Development Research Center, Isfahan University of Medical Sciences, Isfahan, IR Iran
                [2 ]Isfahan University of Medical Sciences, Isfahan, IR Iran
                [3 ]Al-Mahdi University, Isfahan, IR Iran
                [4 ]Department of Epidemiology and Biostatistics, School of Health, Isfahan University of Medical Sciences, Isfahan, IR Iran
                [5 ]NICU Ward, Al-Zahra Hospital, Isfahan University of Medical Sciences, Isfahan, IR Iran
                Author notes
                [* ]Corresponding Author: Amir Mohammad Armanian, Department of Pediatrics, Child Growth and Development Research Center, Isfahan University of Medical Sciences, Isfahan, IR Iran. Tel: 98-9131294044, E-mail: armanian@ 123456med.mui.ac.ir
                Article
                10.5812/ircmj.12559
                4221998
                82b97ccc-8aeb-460a-9065-bb2c02ab9c11
                Copyright © 2014, Iranian Red Crescent Medical Journal; Published by Kowsar Corp.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 May 2013
                : 19 November 2013
                : 25 February 2014
                Categories
                Research Article

                Medicine
                apnea of prematurity,premature infant,methyl xanthine therapy,aminophylline
                Medicine
                apnea of prematurity, premature infant, methyl xanthine therapy, aminophylline

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