Association between gastroesophageal reflux and pathologic apneas in infants: a systematic review

Abstract

To perform a systematic review using PubMed, EMBASE and Cochrane databases to determine whether an association between GER and apnea in infants exists. Studies with n ≥ 10 infants, aged <12 months, were included. GER had to be studied by pH-metry or pH-impedancemetry. GER episodes were defined as pH <4 for ≥ 5 s and/or a drop of >50% of baseline in impedance signal in distal channels. An apneic event was defined as a cessation of breathing for >20 s, or ≥ 10 s with hypoxemia or bradycardia. An epoch of ≤ 2 min was used to define temporal relation between GER and apnea. Methodological quality of studies was assessed with Newcastle Ottawa Scale (NOS). Of 1959 abstracts found, 6 articles met the inclusion criteria. All studies had poor methodological quality. A total of 289 infants were included. The temporal association of GER followed by apnea was assessed in all studies, with epochs varying from 10 s to 2 min. One study found an increase of apneic events after GER, the remaining 5 studies did not find an association. Two studies assessed apnea followed by GER as well, but did not find sufficient evidence for association. This systematic review showed insufficient evidence for an association between GER and apneas in infants. High quality studies using uniform inclusion criteria, definitions according to accepted guidelines, and patient relevant outcome measures are needed.

Cardiorespiratory events in infants with gastroesophageal reflux symptoms: Is there any association?

“…These data suggest that the associations between CR and GER events are more frequent in subjects with more severe GER, but they do not supply information on the causal nature of this relationship. Otherwise, no differences comparing the frequency of CR events between positive and negative SAP group was observed, this suggesting that GER could be relevant in triggering CR events but could not be considered the main mechanism, as previously assessed by other authors . Hasenstab and Jadcherla demonstrated that ineffective pharygoesophageal motility could determine the occurrence of respiratory events in infants with Apparent Life Threatening Event (ALTE) .…”

“…Numerous studies have been published on the relationship between CR and GER events in infants, and on the nature of this relationship, but these studies have reported conflicting results . These studies are difficult to compare for many reasons: methodological differences in the techniques used to identify CR and GER events, differences in the age and characteristics of the study population, in the time window used to define an association of events, and in the definition of CR events . Moreover, CR and GER events may be temporally associated by chance rather than by causality, due to the frequency of both events in infants .…”

“…6,12,13,[15][16][17]26,27 These studies are difficult to compare for many reasons: methodological differences in the techniques used to identify CR and GER events, differences in the age and characteristics of the study population, in the time window used to define an association of events, and in the definition of CR events. 28 Moreover, CR and GER events may be temporally associated by chance rather than by causality, due to the frequency of both events in infants. 18 Most of the studies on the relationship between CR and GER events analyzed the temporal relationships considering all CR and GER events from the study sample as a single pool of data, without performing per-patient analyses.…”

“…Gestational age (weeks) 29 (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38) 38 (34)(35)(36)(37)(38)(39)(40) .073…”

Widespread use of gastric acid inhibitors in infants: Are they needed? Are they safe?

“…Studies have also failed to find any association between GOR and cardiorespiratory events including apnoea, bradycardia, and oxygen desaturation in preterm infants[12,13]. Even so, two thirds of neonatologists have reported using GOR medications to treat apnoeas[14].…”