PEDIATRICS Vol. 116 No. 5 November 2005, pp. 1217-1218 (doi:10.1542/peds.2005-0726)
COMMENTARY |
Apnea Is Not Prolonged by Acid Gastroesophageal Reflux in Preterm Infants
Division of Neonatology,
Department of Pediatrics,
University of Miami School of Medicine,
Miami, FL 33129
Abbreviations: GER, gastroesophageal reflux
Because of the possible association between gastroesophageal reflux (GER) and apnea in preterm infants, a large number of these infants receive treatment for GER with the expectation that it will reduce the frequency or severity of the apnea episodes.1 This is based on data from a few studies, most of them with small numbers of subjects. Most recent studies have shown no clear association between apnea of prematurity and GER and no beneficial effects of anti-GER therapy on the incidence or severity of apnea.2–7
Another indication for GER therapy is based on the possible association between reflux and chronic lung disease. Although it is possible that GER may predispose one to chronic aspiration and secondary lung damage, no clear association between GER and bronchopulmonary dysplasia has been established. Furthermore, no studies have shown conclusively that GER therapy reduces the incidence or severity of bronchopulmonary dysplasia.8,9
GER is a normal physiologic event occurring at all ages and in the majority of preterm infants and, in most instances, is related to transient esophageal sphincter relaxation. This relaxation may be increased during episodes of apnea or by the use of drugs such as caffeine and aminophylline.
The pharmacologic management of GER includes the use of prokinetics and acid-reducing agents. Unfortunately, none of these therapies has been carefully evaluated for safety and efficacy in preterm infants, and both may be associated with significant undesirable adverse effects.
Erythromycin can improve gastroduodenal contractility and improve gastric emptying but may be associated with hypertrophic pyloric stenosis.10,11 Cisapride can also improve gastrointestinal motility and may reduce GER, but it can produce severe cardiac arrhythmias and, in some studies, has been shown to delay gastric emptying in preterm infants.12
There are few data on the pharmacology and effectiveness of acid-reducing agents in preterm infants, and this therapy may be associated with small bowel bacteria overgrowth and increased risk of sepsis,13 increased serum gastrin with increased risk of pyloric stenosis, and altered digestion as a result decreased activity of acid-dependent lipases.
The same is true for surgical antireflux procedures. It is doubtful that the operative risks and permanent consequences of antireflux surgery are justified as treatment for a maturational condition that is physiologic and usually self-limited unless the reflux is severe and clearly associated with major morbidity.
In this issue of Pediatrics, Di Fiore et al14 reaffirm the lack of relationship between GER and apnea in premature infants. In a careful study of >6000 episodes of GER in premature infants, the investigators showed that, contrary to their hypothesis, only 1% of GER episodes was associated with apnea, and there was no difference in apnea rate or duration before or during the GER episodes. In fact, they found a decrease in apnea rate immediately after the GER episodes, possibly because of behavioral arousal caused by the reflux. GER episodes had no effect on the lowest oxygen saturation or heart rate during apnea.
These conclusive data confirm the results from previous studies showing that GER does not contribute to episodes of apnea and hypoxemia in preterm infants. Although it is not always clear how new knowledge gets translated into changes in practice patterns, it is hoped that the results from this study will dissuade clinicians from using anti-GER therapy to reduce apneic episodes in preterm infants.
Let's be reminded that there are maturational processes for which time is the best and safest therapy.
 |
FOOTNOTES |
|---|
Accepted Mar 28, 2005.
Address correspondence to Eduardo Bancalari, MD, Department of Pediatrics, University of Miami School of Medicine, PO Box 016960, Miami, FL 33101. E-mail: ebancalari{at}miami.edu
No conflict of interest declared.
|
REFERENCES |
|---|
 TOP REFERENCES |
|---|
- Dhillon AS, Ewer AK. Diagnosis and management of gastro-oesophageal reflux in preterm infants in neonatal intensive care units. Acta Paediatr. 2004;93 :88 –93[CrossRef][Web of Science][Medline]
- Peter CS, Sprodowski N, Bohnhorst B, Silny J, Poets CF. Gastroesophageal reflux and apnea of prematurity: no temporal relationship.
Pediatrics. 2002;109
:8
–11
[Abstract/Free Full Text] - Poets CF. Gastroesophageal reflux: a critical review of its role in preterm infants. Pediatrics. 2004;113 (2). Available at: www.pediatrics.org/cgi/content/full/113/2/e128
- Suys B, De Wolf D, Hauser B, Blecker U, Vandenplas Y. Bradycardia and gastroesophageal reflux in term and preterm infants: is there any relation? J Pediatr Gastroenterol Nutr. 1994;19 :187 –190[Medline]
- Arad-Cohen N, Cohen A, Tirosh E. The relationship between gastroesophageal reflux and apnea in infants. J Pediatr. 2000;137 :321 –326[CrossRef][Web of Science][Medline]
- Khalaf MN, Porat R, Brodsky NL, Bhandari V. Clinical correlations in infants in the neonatal intensive care unit with varying severity of gastroesophageal reflux. J Pediatr Gastroenterol Nutr. 2001;32 :45 –49[CrossRef][Web of Science][Medline]
- Kimball AL, Carlton DP. Gastroesophageal reflux medications in the treatment of apnea in premature infants. J Pediatr. 2001;138 :355 –360[CrossRef][Web of Science][Medline]
- Akinola E, Rosenkrantz TS, Pappagallo M, McKay K, Hussain N. Gastroesophageal reflux in infants < 32 weeks gestational age at birth: lack of relationship to chronic lung disease. Am J Perinatol. 2004;21 :57 –62[CrossRef][Web of Science][Medline]
- Sindel BD, Maisels MJ, Ballantine TVN. Gastroesophageal reflux to the proximal esophagus in infants with bronchopulmonary dysplasia.
Am J Dis Child. 1989;143
:1103
–1106
[Abstract/Free Full Text] - Hauben M, Amsden GW. The association of erythromycin and infantile hypertrophic pyloric stenosis: causal or coincidental? Drug Saf. 2002;25 :929 –942[CrossRef][Medline]
- Cooper WO, Griffin MR, Arbogast P, Hickson GB, Gautam S, Ray WA. Very early exposure to erythromycin and infantile hypertrophic pyloric stenosis.
Arch Pediatr Adolesc Med. 2002;156
:647
–650
[Abstract/Free Full Text] - McClure RJ, Kristensen JH, Grauaug A. Randomized controlled trial of cisapride in preterm infants.
Arch Dis Child Fetal Neonatal Ed. 1999;80
:F174
–F177
[Abstract/Free Full Text] - Basaran UN, Celayir S, Eray N, Ozturk R, Senyuz OF. The effect of an H2-receptor antagonist on small-bowel colonization and bacterial translocation in newborn rats. Pediatr Surg Int. 1998;13 :118 –120[CrossRef][Medline]
- Di Fiore JM, Arko M, Whitehouse A, Kimball A, Martin RJ. Apnea is not prolonged by acid gastroesophageal reflux (GER) in preterm infants.
Pediatrics. 2005;116
:1059
–1063
[Abstract/Free Full Text]
PEDIATRICS (ISSN 1098-4275). ©2005 by the American Academy of Pediatrics
CiteULike 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  L Corvaglia, D Zama, S Gualdi, M Ferlini, A Aceti, and G Faldella Gastro-oesophageal reflux increases the number of apnoeas in very preterm infants Arch. Dis. Child. Fetal Neonatal Ed., May 1, 2009; 94(3): F188 - F192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Journal Watch Arch. Dis. Child., April 1, 2006; 91(4): 371 - 372. [Full Text] [PDF]
|
|
|
|
|
|
Journal Watch Arch. Dis. Child., March 1, 2006; 91(3): 274 - 275. [Full Text] [PDF]
|
|
|
|
 |
|
 Gastroesophageal Reflux and Apnea in Premature Infants Journal Watch Pediatrics and Adolescent Medicine, November 28, 2005; 2005(1128): 5 - 5. [Full Text]
|
|
|
|
 |
|
 Gastroesophageal Reflux and Apnea in Premature Infants Journal Watch (General), November 11, 2005; 2005(1111): 6 - 6. [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
