Gastroesophageal reflux (GER) is defined as the retrograde movement of gastric contents into the esophagus with or without regurgitation. Uncomplicated GER is a normal physiologic process in infants, in part due to relatively large liquid volumes ingested during feedings and supine positioning which places the gastroesophageal junction in a liquid environment. Uncomplicated GER should not prompt further investigation or treatment. However, when reflux of gastric contents is associated with troublesome clinical symptoms or signs, it is called gastroesophageal reflux disease (GERD). In clinical practice, since “troublesome signs” in newborns, especially those born prematurely, are most often non-specific and subjective, it is difficult to differentiate GER from GERD; as a result these terms are frequently used interchangeably by medical professionals and parents alike.1 The difficulty in making a diagnosis of GERD in premature newborns can lead to its over diagnosis and treatment, as well as significant practice variation.2 In one study of 33 academic children’s hospital Newborn Intensive Care Units (NICU), there was a 13-fold variation (2 to 26 %) in the diagnosis and treatment of GERD in NICU patients.3 In this study, patients with a GERD diagnosis had longer hospital stays and costs than infants without this diagnosis. In addition, infants discharged from the NICU on anti-reflux medications frequently remain on treatment for many months after discharge, making it an important clinical entity in the NICU and beyond.4

Preterm infants are at increased risk for reflux in part due to gastrointestinal dysmotility and delayed gastric emptying affected by immaturity.5 In addition, nearly all preterm infants <30 weeks’ gestational age are diagnosed with apnea of prematurity, and since most also have reflux, a causal relationship between reflux and apnea of prematurity has been commonly hypothesized. Studies to elucidate a temporal relationship between reflux and apnea, however, have yielded conflicting results. Despite this uncertainty, premature infants frequently are diagnosed with GERD, with apnea and bradycardia a suspected clinical sign.2 This article will review the physiologic rationale for a possible causal link between apnea of prematurity and reflux, and review studies of their possible temporal relationship.