GI Educational Cartoons For Children

Diana Lerner and the Medical College of Wisconsin have developed additional GI educational videos.  Previously, they had developed cartoon videos explaining endoscopy (prev post: Terrific Educational Videos on Endoscopy).  Now there are several more.  All of these are in English and some in Spanish.

Topics include inflammatory bowel disease, gastroesophageal reflux, eosinophilic esophagitis, and celiac disease.

Here’s the link:  Pediatric Gastroenterology Cartoons For Kids

Related blog post:



Pacifiers & Reflux in Preterm Infants Plus Swallow Syncope

In a crossover study (J Pediatr 2016; 172: 205-8) with 30 preterm infants (adjusted age 33 weeks at time of study) showed that non-nutritive sucking with a pacifier had no effect on acid and nonacid gastroesophageal reflux based on esophageal pH-impedance.

My take: It is good that sucking a pacifier did not effect reflux.  What would the authors have proposed if it had?

Another curious report: “Syncope with Swallowing” J Pediatr 2016; 172: 209-11.  Case report of a teenager who had syncope with drinking and eating along with atrial septal defect; after repair of ASD, the symptoms persisted and ultimately the patient had a pacemaker placed due to an exaggerated vagoglossopharyngeal reflex leading to high-grade AV block.

Gibbs Gardens

Gibbs Gardens

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

Selective Data Mining: Reflux and Bronchopulmonary Dysplasia

With some studies, the abstract may suggest a more compelling result than is truly evident.  That’s how I feel about a recent report (Nobile S, et al. J Pediatr 2015; 167: 279-85).

Here’s the conclusion (verbatim) from the abstract: “The increased number of (and sensitivity for) pH-only events among infants with BPD may be explained by several factors, including lower milk intake, impaired esophageal motility, and a peculiar autonomic nervous system response pattern.”

To me, it sounds like this prospective study of pH-multichannel intraluminal impedance (pH-MII) of 46 infants born ≤32 weeks gestation (12 with bronchopulmonary dysplasia (BPD) and 34 without BPD) must have identified something important linking gastroesophageal reflux disease (GERD) and BPD.  But, the real findings, in my view, are that this is a negative study. Period.

Here are the results reported in the abstract:

  • “Infants with BPD…had increased numbers of pH-only events (median number 21 v 9) and a higher symptom symptom sensitivity index for pH-only events (9% vs. 4.9%)”
  • They also state: “the number and characteristics of acid, weakly acid, nonacid and gas gastroesophageal reflux events, acid exposure, esophageal clearance, and recorded symptoms did not significantly differ between the 2 groups.”

Here’s a little more data –not in the abstract:

  • The P value for the difference in pH-only events was .360
  • The authors could just have easily pointed out (in the abstract) that infants without BPD had increased acid exposure: 40.5 min compared with 27.0 min (P = .599)

What should have been in the abstract conclusion? Perhaps, the first line of their discussion: “Infants with BPD did not have significantly higher GER features compared with infants without BPD as measured by esophageal pH-MII monitoring, except for higher occurrence of pH-only events and higher SSI for pH-only events.”

The authors try to explain the differences in the BPD patients by highlighting some of the potential mechanisms of reflux and/or autonomic dysfunction.  I think the limitations of this study deserve careful scrutiny.  This was a small study with only 12 BPD infants.  There was a significant selection bias -only ‘symptomatic’ infants were included.  Some of the factors affecting BPD directly could have an indirect effect on reflux (eg. caffeine).

The authors make one other point: “we believe pharmacologic treatment for GER should be initiated only after the demonstration of pathologic pH-MII monitoring to avoid unnecessary drug therapy, adverse events, and costs.”

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Grand Prismatic Spring, Yellowstone

Grand Prismatic Spring, Yellowstone

pH Probe Testing: Rumors of My Death are Premature

Several years ago, an “obituary” was written for the pH probe (Putnam PE,J Pediatr.  2010; 157(6):878-80) due to the presumed superiority of pH-impedance (pH-MII) studies in detecting gastroesophageal reflux disease (GERD)  As noted in previous blogs (see below), there have remained a number of concerns with the assumption that pH-MII is an improvement over pH studies without impedance.  Several recent studies elaborate on those concerns:

  1. Cheng F-K F, et al. Clin Gastroenterol Hepatol 2015; 13: 867-73
  2. Patel A, et al. Clin Gastroenterol Hepatol 2015; 13: 884-91
  3. Vaezi MF. Clin Gastroenterol Hepatol 2015; 13: 892-94 (editorial)

In the first study, the authors identified 221 patients and retrospectively reviewed GERD testing from 2006-2011.  Prior to testing, 97% had received prescribed PPIs before testing; however, PPIs were discontinued for at least 1 week prior to evaluation which included upper endoscopy, esophageal manometry, and pH-MII.

  • 21 (10%) had erosive esophagitis
  • 61 (27%) had nonerosive reflux disease with increased pH
  • 18 (8%) had nonerosive reflux disease with abnormal impedance
  • 30 (14%) had hypersensitive esophagus
  • 18 (8%) had functional heartburn
  • 30 (14%) had other functional disorders
  • 43 (19%) were undetermined

Thus, this retrospective study showed that the majority (roughly 2/3rds) of patients with GERD symptoms on PPI therapy did not have GERD based on objective testing.  The authors chose to test off PPI therapy “because we postulated that the pretest probability of GERD diagnosis was low, primarily given their lack of response to PPI.”

In the second study, 187 subjects (≥18 years) underwent pH-MII testing in a prospective study from 2005-2010.  49.7% were tested off proton pump inhibitor therapy. Abnormal acid exposure time consistently predicted symptomatic outcome.  The authors note that performing pH-MII off PPI therapy best predicts response to antireflux therapy

In the third reference, the editorial which commented on the second, there are several useful points:

  • “There is little doubt that pH-impedance testing provides a more sensitive means of comprehensively identifying reflux events in a given patient. However, to date, studies have failed to demonstrate that it provides any significant additional clinical benefit.”
  • “Caution must be exercised when incorporating the added objective data from non-acidic or weakly acidic reflux events into treatment decision-making…Studies including Patel et al have not shown that knowledge regarding continued non-acid or weakly acid reflux events alter patient outcomes.”
  • “Wireless pH testing is generally better tolerated and provides longer measurement duration”
  • The use of symptom indices are too subjective.  “Recent data question the use of these indices especially in those with refractory symptoms and minimal reflux by pH or impedance testing.”  SI and SAP could be altered by chance occurrences….”A colleague expert in esophageal diseases …once said: “I know the tests are no good but I don’t know what else to use.'”
  • “Let us simplify our approach on the basis of available data and not use measures that we know are suboptimal at best.”

After looking at these studies and the previous pH probe obituary, I’m reminded of a story.  Several religious leaders were asked what they wanted someone to say at their funeral.  A few stated that they wanted their congregants/flock to comment on their values, like piety and charity.  However, one said, “I hope they say, ‘Look he’s moving!'”

Bottomline: There is no reliable evidence that pH-MII testing improves outcomes over conventional pH probe testing. In fact, the use of pH-MII, by lowering the specificity for GERD, could have a detrimental effect.  With either test, holding acid suppression for 1 week (with PPIs) is likely to be helpful in interpreting the results.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Zoo Atlanta

Zoo Atlanta

No Effect of Proton Pump Inhibitors and Irritability on Crying in Infants

While the title of this blog will come as no surprise to most pediatric gastroenterologists, many parents would be surprised that a systemic review of randomized controlled trials (RCTs) showed` that proton pump inhibitors (PPI) are ineffective for crying infants (J Pediatr 2015; 166: 767-70).

In this review, only five trials (with 430 infants) met the prespecified inclusion criteria.  While some trials showed a decrease in crying/irritability form baseline to the end of the intervention, a similar effect was evident in the control group.  The authors found that one trial reported a higher risk of lower respiratory tract infections in the PPI group and note that “administration of PPIs is not without risk.”

Take-home message: “the limited data available suggest that PPIs are not effective for the management of crying/irritability in infants.”

Another PPI citation: Rosen R et al. J Pediatr 2015; 166: 917-23.  In this study, the authors prospectively showed that PPI use was associated with differences in gastric, lung, and oropharyngeal microflora (n=116 children with 59 receiving PPIs)

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Transoral Fundoplication for Refractory Gastroesophageal Reflux

A new endoscopic technique’s efficacy has recently been reported (Gastroenterol 2015; 148: 324-33).  Since this technique is not likely to be broadly applicable to the pediatric population for some time, I will not delve into all of the details.

In essence, a carefully selected group (n=129 from a screened group of 696) of adult patients with persistent regurgitation underwent transoral fundoplication; this eliminated troublesome regurgitation in 67% compared to 45% who were randomized to sham/PPI.  Severe complications were rare.

Here is a picture of the technique:

Transoral Fundoplication

Transoral Fundoplication

Link: Description and a video animation of the procedure

Bottomline: This endoscopic procedure along with the Stretta procedure and the LINX device (using magnets) offer alternatives to surgical fundoplication in carefully-selected patients with refractory gastroesophageal reflux symptoms.

New drugs approved by FDA:

Ceftolozane (Zerbaxa) -combines a cephalosporin with a beta-lactamase inhibitor (tazobactam).  Indications: complicated intra-abdominal infections (in combination with metronidazole), and complicated urinary tract infections. From FDA: FDA approves new antibacterial drug Zerbaxa

Viekira Pak -combination of 3 new drugs: ombitasvir, paritaprevir, and dasabuvir along with  older drug: ritonavir.  Indications: Hepatitis C genotype 1. From FDA: FDA approves Viekira Pak to treat hepatitis C

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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.

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Accuracy of ENT diagnosis of Reflux Changes

Many gastroenterologists suspiciously view a diagnosis of laryngopharyngeal reflux (LPR) as assessed by an Ear, Nose, and Throat (ENT or otorhinolaryngologist) physician.  This is due to a high degree of variability of these visible findings in a number of studies.  A recent pediatric study reaches the same conclusion (J Pediatr 2014; 165: 479-84).

In this study, the authors recruited 52 infants in an effort to establish a reflux finding score for infants (RFS-I).  This infant scale was modified based on a previous RFS developed in adults (Laryngoscope 2001; 111: 1313-7).  In these infants, scored videos were evaluated by 3 pediatric ENTs, 2 adult ENTs, and 2 gastroenterology fellows.

Specific finding:

  • “laryngeal erythema/edema showed the lowest observer agreement…it is often speculated that laryngeal edema is caused by LPR, but no convincing evidence is available to support this theory.”

Bottomline: “Only moderate interobserver agreement [of the RFS-I] was reached with a highly variable intraobserver agreement…the RFS-I and flexible laryngoscopy should not be used solely to clinically assess LPR related findings of the larynx, nor to guide treatment.”

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Clinical Features of 22q11.2 Deletion Syndrome

Since I participate in the 22q Specialty Clinic in Atlanta, I am interested in relevant clinical studies.  A recent study provides more information on clinical features and follow-up (J Pediatr 2014; 164: 1475-80).

This retrospective and prospective multicenter study involved 228 patients.  The median age at diagnosis was 4 months.  In 71% the diagnosis was made before age 2 years and predominantly related to congenital heart disease and neonatal hypocalcemia.

Key findings:

  • The survival probability was 0.92 at 15 years from diagnosis, most commonly from severe cardiovascular complications.  Two subjects died without cardiac defects, one with severe autoimmune anemia and the second with lymphoproliferative disease.
  • Congenital heart disease was confirmed in 79% of the entire cohort.
  • Neonatal hypocalcemia was noted in 43%
  • ENT manifestations were present in 59% and included most commonly velopharyngeal insufficiency
  • GI manifestations were noted in 41%, particularly feeding difficulties in infancy.  Anorectal malformations were identified in 5% and esophageal atresia was noted in 1%.  GI problems tended to improve during followup, particularly gastroesophageal reflux.  During followup, three children with abdominal pain (along with leg pain) had mild hypocalcemia.
  • Autoimmune manifestations developed in 11%, most commonly autoimmune thrombocytopenia.

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Link: Practice guidelines for 22 q (from UC Davis Website and J Pediatr. 2011 Aug;159(2):332-9.e1. doi: 10.1016/j.jpeds.2011.02.039).