Gastroesophageal Reflux in Preterm Infants: How Acid Should It Be?

To the Editor: The interesting article by Omari et al ⁽¹⁾ in the January 2007 issue of the Journal regarding the effect of the proton pump inhibitor (PPI) omeprazole on acid production in newborns with gastroesophageal reflux prompts several considerations concerning the diagnosis and treatment of this condition.

Preterm infants are often discharged on antisecretory therapy for a number of indications despite scarce evidence of the benefit of this approach. In fact, although gastroesophageal reflux disease (GERD) is thought to cause feeding problems, apnea, desaturation, bradycardia, and stridor, it can be difficult to diagnose in infants mainly because frequent feeds neutralize stomach contents. This may explain the lack of agreement as to the diagnostic cutoff level of the reflux index for preterm babies ⁽²⁾, which in various studies ranges between 5% and 10% ⁽³⁾. It is conceivable that the discrepancy between normalization of acid reflux and lack of effect on symptoms after PPI treatment reported by Omari and coworkers could reflect the fact that 8 of the 10 infants they evaluated had a reflux index >5% but <7%. In fact, using the intraluminal impedance technique, López-Alonso et al ⁽⁴⁾ recently reported that the esophagus can be exposed to acid 5% of the time in more than 50% of healthy preterm infants ⁽⁴⁾, and consequently this cutoff level may lack specificity for GERD diagnosis. Moreover, we found that 7 preterm babies (mean postmenstrual age <36 weeks) who developed severe symptomatic GERD (reflux index >20%) after surgery for esophageal atresia responded well to PPI in a long-term follow-up (>3 months) (unpublished data).

As suggested by Omari et al, their infants may not have responded clinically to antisecretory therapy because they had a minor acidic disease, and their symptoms may have been due to weakly acidic refluxes, which coincides with our recent findings obtained in preterm infants with apnea of prematurity ⁽⁵⁾. Alternatively, or additionally, a lack of clinical response to omeoprazole could be related to the different ages of the infants studied by Omari and colleagues. The gestational age of some of them well exceeded the premature threshold. In others, pH was measured at a time when their corrected mean postmenstrual age was also beyond full term.

The above considerations highlight the need to establish an age-related diagnostic reflux index to identify infants affected by GERD to spare them unnecessary and possibly harmful treatment. Indeed, as concluded by Omari and colleagues, infants with signs of GERD will not necessarily benefit from treatment with antisecretory drugs. At present, because the prolonged use of acid inhibitors in preterm infants significantly increases the risk of infections ⁽⁶⁾, they should be prescribed only for neonates with relevant clinical evidence of disease, namely in cases of gastroesophageal reflux after surgery for esophageal atresia and neonates with severe GERD.