Your neonatologist colleague is caring for a 3-week-old former 28-week infant on nasal cannula oxygen and caffeine therapy for apnea of prematurity in the neonatal intensive care unit (NICU). On rounds one morning, a nurse comments that the recurrent apnea episodes appear worse, and the baby is frequently irritable and difficult to settle after a feeding.
Discussion ensues as to whether these signs might be attributable to gastroesophageal reflux (GER). The neonatologistsuggests that a trial of a histamine-2 (H-2) receptor blocker might be indicated to see if the signs improve since they might be due to acid reflux.
GER is diagnosed frequently in premature infants, but treatment varies greatly across NICUs. H-2 blockers and proton pump inhibitors are used widely despite a 2015 report that identified the routine use of anti-reflux medications in preterm infants as a therapy of questionable value as part of the Choosing Wisely campaign (http://bit.ly/2rMjFZ9).
A new clinical report from the AAP Committee on Fetus and Newborn addresses up-to-date methods to diagnose clinically significant GER in the preterm infant and whether commonly ascribed signs, such as recurrent apnea, feeding intolerance or postprandial irritability, are temporally related to GER. Also addressed is whether common treatment modalities — both pharmacologic and nonpharmacologic — are effective in reducing these clinical signs.
The report Diagnosis and Management of Gastroesophageal Reflux in Preterm Infantsis available at https://doi.org/10.1542/peds.2018-1061 and will be published in the July issue of Pediatrics.
GER is extremely common in preterm infants, occurring multiple times every day due to reflex relaxation of the lower esophageal sphincter. While diagnostic methods are available to assess both acidic and non-acidic GER in infants, most babies in the NICU are diagnosed based on a constellation of signs thought attributable to GER. However, when carefully evaluated with multichannel intraesophageal impedance combined with pH measurements in the lower esophagus, the vast majority of reflux episodes in neonates are non-acidic.
In addition, several studies have shown that behavioral signs frequently thought to be due to GER are only rarely associated with actual measured episodes. Furthermore, there is little evidence to support a temporal relationship between apnea of prematurity and GER.
More importantly, use of acid blockade in premature infants has been associated with a higher risk of necrotizing enterocolitis, late onset sepsis and even death. Other medications to enhance gastric motility (e.g., metoclopramide) also have been associated with complications and have not been demonstrated to be a useful therapy.
These data led to the following recommendations for clinicians caring for preterm infants:
- Signs commonly ascribed to GER in preterm infants include feeding intolerance or aversion, poor weight gain, frequent regurgitation, apnea, desaturation, bradycardia, irritability and perceived postprandial discomfort. Data do not support the temporal association of these perceived signs of GER with either acidic or nonacidic reflux episodes as measured by multichannel intraesophageal impedance/pH, and the signs usually will improve without treatment.
- Preterm infants with clinically diagnosed GER often are treated with pharmacologic agents; however, a lack of efficacy together with emerging evidence of significant harm (particularly with gastric acid blockade) strongly suggest that these agents should be used sparingly, if at all, in preterm infants.
- Nonpharmacologic measures to control reflux, such as placing the infant in the left lateral position, elevating the head, feeding smaller volumes more frequently and using thickened formula have not been shown to reduce clinically assessed signs of GER in the preterm infant. For infants older than 32 weeks’ postmenstrual age, safe sleep recommendations, including avoidance of commercial devices that elevate the baby’s head in the crib, should be modeled for parents as hospital discharge approaches.
The clinical report should help guide clinicians to “just say no” to the treatment of GER in the NICU.
Dr. Eichenwald, the lead author of the clinical report, is a member of the AAP Committee on Fetus and Newborn.
