How Likely is Reflux in Infants with “Reflux-like” Behaviors?

Another study (Funderburk et al. JPGN 2016; 62: 556-61) has shown that gastroesophageal reflux disease is infrequent in infants with a “strong clinical suspicion for reflux.”  This is a good to know since we also know that pharmacologic therapy for gastroesophageal reflux has not been proven to be effective in infancy either.

This retrospective study with 58 infants, including 40 preterm infants, evaluated for GERD with MII-pH studies.  Characteristics of cohort: median gestational age 31 weeks, median birth wt 1683 gm, and median age at study: 70 days. 10 patients were receiving acid suppression therapy.

Indications for testing:

  • Irritability 55%
  • Bradycardia  34%
  • Desaturation 31%
  • Cough 21%
  • Gagging 12%
  • Difficulty feeding 12%
  • Arching 10%
  • Apnea 5%

Key findings:

  • Only 6 infants (~10%) had abnormal MII-pH studies (defined as >95th percentile for reflux episodes/hours or >95th percentile for acid exposure time)
  • None of the symptom indices correlated with symptoms. SI, SSI, or SAP
  • The majority of reflux episodes did not correlate with clinical “reflux” behaviors
  • Small bore (5 Fr) NG tubes were not associated with increased reflux.

In the related commentary by Rachel Rosen (pgs 517-18), she noted that “there is little to no evidence to show that the 3 indices predict any meaningful clinical outcome…including response to fundoplication, or medications.” “The current literature fails to support the use of symptom indices to prove causality when resolution of symptoms with medical or surgical therapies is used as the criterion standard.”

My take: The vast majority of infants with “reflux behaviors” do not have reflux.  Even if they do, current pharmacologic therapies have not been shown to work.  So, there is little  value in reflux testing in most infants.  Finally, given the failure of symptom indices, does the addition of the impedance data to the pH data add any value?

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Jerusalem Collage -Made from hundreds of postcards.  Vik Muniz

Jerusalem Collage -Made from hundreds of pictures/postcards. Look closely -it’s amazing.  by Vik Muniz

Hyperbilirubinemia and Central Apnea

Briefly noted: “Unbound Unconjugated Hyperbilirubinemia is Associated with Central Apnea in Premature Infants” J Pediatr 2015; 166: 571-5.  This was a prospective observational study with 100 27-33 gestational infants.  The group with central apnea had higher unconjugated hyperbilirubinemia (UB).  The authors speculate that UB could cause neurotoxicity via central chemoreceptors and more aggressive treatment of UB with phototherapy could be needed.

Which is Safer –Drip Feeds or Bolus Feeds in Healthy Preterm Infants?

A recent provocative study (J Pediatr 2014; 165: 1255-7) takes a look at the frequency of cardiorespiratory events in healthy neonates <33 weeks gestation who needed supplemental enteral tube feeds.

It is generally accepted that continuous or “drip” feedings are less likely to provoke reflux events (and reflux-induced cardiorespiratory events) by limiting the amount of formula in the stomach at any time point.  If there is less formula, presumably there would be less stomach distention and a lower likelihood of reflux.  In addition, a continuous amount of formula would serve to buffer stomach acid.

Despite the sound theoretical underpinnings, is this really true?  In this study, the authors detected fewer cardiorespiratory events with polysomnographic monitoring in healthy premature neonates who were fed with bolus feedings rather than with drip feedings.

Study design: Each of 33 infants served as its own control.  During a 6-hour monitoring period, noninvasive polysomnographic recordings were performed.  Each infant was fed twice via an orogastric tube.  The first meal was given as a 10-minute bolus (by gravity) and the second was delivered over 3 hours. It is noted that the tube was removed after the bolus feeding (this is not routinely done in clinical practice).

Demographics: Median gestational age was 31 weeks and median postnatal age was 16 days.  Fortified human milk was given in 12, premature formula in 7, and 14 had mixed feeding.

Results (Table 2): “continuous feeding was associated with a greater number of prolonged apneas and apnea-related hypoxic episodes.”

  • Median Apnea Frequency: 4 in continuous versus 2 in bolus group (no obstructive apneas were noted)
  • Median hypoxic episodes: 3 in continuous versus 2 in bolus group.

The authors speculate that leaving the tube in place for continuous feeds could increase GER-related apnea or trigger ‘protective upper airway reflexes in response to the irritating stimulus.’

Bottomline: The assumption that continuous feedings will reduce cardiorespiratory events is not supported by this study.  The findings warrant cautious interpretation; the small sample size and specific ages of the premature infants are significant limitations.   In addition, leaving an enteral tube in place after a bolus feeding would be a better design as this is a routine practice.

Related blog post:

What to do with ALTEs?

While apparent life-threatening events (ALTEs) in infants are quite disturbing, the best management for these events is far from clear. A recent systematic review of ALTEs in infants was undertaken and included studies from 1970-2011 (J Pediatr 2013; 163: 94-9). The authors ultimately identified 37 relevant studies: 18 prospective observational studies and 19 retrospective observational studies.


  • None of the 37 studies yielded “a high level of evidence for diagnostic or prognostic investigations.”
  • Risk factors for ALTE: prematurity, previous ALTEs, and suspected child maltreatment.
  • Routine screening for gastroesophageal reflux, meningitis, bacteremia, and seizures are “highly unlikely to be helpful in patients who are well-appearing and have no other findings suggestive of a diagnosis.”
  • Testing for GERD “is unnecessary in children with ALTEs.”  “A positive test does not necessarily inform management because causation cannot be established.”  Patients with recurrent ALTEs “may benefit from pH monitoring in combination with symptom recording.

Additional references:

NASPGHAN Consensus guidelines on GERD (2009)

Link: Gastroesophageal Reflux Disease in the Pediatric  – NASPGHAN.o

  • In premature infants, a relationship between GER (i.e. reflux) and pathologic apnea and/or bradycardia has not been established.Despite a lack of convincing evidence, if pathological apnea occurs in the face of pre- existing reflux, then the following two statements are the most common features:
  • Although reflux causes physiologic apnea, it causes pathologic apneic episodes in only a very small number of newborns and infants.
  • When reflux causes pathological apnea, the infant is more likely to be awake and the apnea is more likely to be obstructive in nature.
  • A diagnosis of an acute life-threatening event (ALTE) warrants consideration of causes other than GER (i.e. reflux).Reflux of gastric acid seems to be related to ALTEs (episodes of combinations of apnea, color change, change in muscle tone, choking, and gagging) in < 5 % of infants with ALTE. 
  • -J Pediatr 2009; 155: 516. Bradycardia not improved in preemies treated for GER. n=18. Editorial 464 urges not using GER Rx in neonates –outside clinical trials.
  • -J Pediatr 2009; 154: 374. Apnea associated with reduction in LES tone in premature infants; therefore, GER may be secondary to apnea rather than the reverse. Small study -12 apneic event in 7 infants.
  • -J Pediatr 2008; 152: 365. Compared risk factors with SIDS. One of 153 (0.6%) with ALTE died.
  • -Pediatrics 2005; 116: 1059 & 1217 (editorial). Apnea in preemies is unrelated to GER.
  • -Pediatrics 2004; 113: e128-132. Apnea is unrelated to GER in most preemies; airway problems due to GERD is hard to establish.
  • -J Pediatr 2000; 137: 321 & 298. Poor temporal association between GER & apnea in ALTE patients.
  • -J Pediatr 2001; 138: 355. Metoclopropramide/cisapride do not help apnea in preemies with GER
  • -Pediatrics 2002; 109: 8-11. GER does not cause apnea of prematurity.