Apnea in preterm neonates: what's the role of gastroesophageal reflux? A systematic review

Dig Liver Dis. 2020 Jul;52(7):723-729. doi: 10.1016/j.dld.2020.03.032. Epub 2020 May 15.


A causal relationship between gastro-esophageal reflux (GER) and apnea in preterm infants has been frequently hypothesized and is currently debated. The present study aims at reviewing the currently available scientific evidence, in order to clarify the role of GER on the occurrence of apnea and to help improving the clinical management of apneic preterm neonates. We performed a systematic literature search to identify all the clinical studies on preterm neonates that properly assessed the relationship between apnea and GER. Two-hundred and fifty-two papers, including 32 reviews and meta-analysis, were screened. Out of them, only 7 were included in the final analysis according to the selected criteria. Among them, 3 studies reported an increased frequency of apnea after reflux compared to reflux-free period and 4 denied a significant temporal relation. In conclusion, a minority of apneic events occurs soon after GER episodes. Whether this happens by chance or because of a causal relationship is still impossible to define. Based on the available data, empirical treatment with acid inhibitors is not recommended in neonates with apnea unless a proven temporal relation is shown by simultaneous esophageal pH-impedance and polysomnography or cardiorespiratory monitoring and in the absence of a clear clinical benefit.

Keywords: Apnea of prematurity; Gastroesophageal reflux; Preterm neonates.

Publication types

  • Systematic Review

MeSH terms

  • Apnea / etiology*
  • Electric Impedance
  • Esophagus*
  • Gastroesophageal Reflux / complications*
  • Humans
  • Hydrogen-Ion Concentration
  • Infant, Newborn
  • Infant, Premature / physiology*