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

In infants, apneas can be centrally mediated, obstructive or both and have been proposed to be gastroesophageal reflux (GER) induced. Evidence for this possible association has never been systematically reviewed.

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.