Category Archives: Pediatric Gastroenterology Intestinal Disorder

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

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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)

Related blog posts:

An Apple a Day …

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According to research, published in JAMA Internal Medicine (April 1st edition –done for fun and “is very tongue in cheek”) an apple a day does not “keep the doctor away.”

Here’s an excerpt from USA Today summary:

At first glance, data on 8,728 U.S. adults looked like it might uphold the saying: The 9% who ate at least one small apple daily were less likely to visit doctors several times a year….They adjusted their statistics to account for ways other than apple-eating that “apple eaters might be very different from everyone else,” Davis says. For example, they found apple lovers were less likely to smoke, were more educated and were less likely to be white than the 91% of the population eating less than an apple a day.

After adjusting for those factors, they found daily apple-eaters were just as likely as otherwise similar individuals to go to doctors…Other studies have found numerous possible health benefits associated with apple consumption, including weight loss, reduced cancer risk and improved cardiovascular health.

UTI in Infancy–New Risk Factor for Chronic Abdominal Pain?

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A recent study (Rosen JM, et al. JPGN 2015; 60: 214-16) identifies a history of a urinary tract infection (UTI) in infancy as a risk factor for development of chronic abdominal pain.

The authors identified 57 patients with a history of UTI during the first year of life and compared them to 58 sibling controls.  Mean age of UTI was 4.8 months and mean time since UTI was 9.3 years.

Key finding:

  • Chronic abdominal pain was noted in 10 (17.5%) of patients with prior UTI compared with 2 (3.4%) of controls (P=0.02)

The authors state that this is the first study showing an infection outside the GI tract could increase the risk of chronic abdominal pain.  It is not clear to me if the UTI would truly be a sensitizing factor or whether other factors like the administration of antibiotics could play a role.

Bottomline: While this is a small study and the incidence of chronic abdominal pain was fairly low in both groups, it suggests that a history of a UTI may be a risk factor for recurrent abdominal pain; a bigger study is needed to validate these findings.

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From Twitter

Trending on Twitter -CampWeeKanEatIt Shoutout

Mongerson -Phase II Data Available in NEJM

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Previously, this blog noted that a phase II study showed that Mongerson, an oral SMAD7 antisense oligonucleotide, had promising data for moderate-to-severe Crohn’s: An Oral Oligonucleotide in the Crohn’s Treatment Pipeline …

The study has now been been published: NEJM 2015; 372: 1104-13.  Among patients who received 40 mg and 160 mg of mongerson, remission (CDAI <150) at 15 days was achieved in 55% and 65% respectively compared to 12% for 10 mg dose and 10% for placebo group.

The associated editorial (pg 1166-67) notes that only 18% of the patients with elevated C-reactive protein and randomized to the 40 mg and 160 mg doses normalized these levels at the end of the treatment period.  Thus, further trials will need to look more closely at objective biomarkers.

Unrelated but interesting -from John Pohl & Bryan Vartabedian’s twitter feeds:  “Food Babe” Exposed as a Fraud

How Likely is Celiac Disease if My TTG Test Is Only a Little Bit Abnormal?

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A terrific celiac serology study (Gidrewicz D, et al.Am J Gastroenterol 2015; -advanced online publication doi: 10.1038/ajg.2015.87) helps answer questions about the utility of serology in making diagnostic decisions. (Thanks to corresponding author J Decker Butzner for sharing reference.)

Using consecutive samples in a laboratory database with 17,505 patients, the authors retrospectively examined the performance of the tissue transglutaminase (TTG), endomysial antibody (EMA) tests and the ESPGHAN celiac guidelines for nonbiopsy diagnosis of celiac disease.  Among this large cohort, 775 with positive TTG and 574 with a negative TTG were biopsied.

Key findings:

  • If the TTG >10-fold the upper limit of normal (ULN) along with a positive EMA and symptoms were present, 98.2% had biopsies consistent with celiac disease.
  • If the TTG was 3-10-fold-ULN along with positive EMA, then 75.7% had biopsies consistent with celiac disease.  The histology of celiac disease (CD) was present in only 40% of the TTG 3-10-fold ULN if EMA was negative.
  • If the TTG was 1-3-fold-ULN along with positive EMA, 52.2% had CD-positive histology, whereas CD-positive histology was evident in only 13.3% of TTG 1-3-ULN if EMA was negative.
  • IgA deficiency is common in CD (“1in 60 vs 1 in 700” in general population)

Implications & Take-home points:

  • The researchers note that the positive predictive value of TTG drops when the prevalence of CD in the testing population is lower.  Thus, in their population and most clinical practice where the prevalence is below 35-40%, the PPV of the TTG-based tests drops to <80%.
  • While TTG-based tests have high specificity, there are multiple medical conditions that can cause a false positive (additional reference below), including autoimmune diseases like diabetes mellitus, inflammatory bowel diseases as well as infections, and liver disorders.
  • Asymptomatic patients with low TTG titers and negative EMA may benefit from following celiac serology rather than proceeding immediately to intestinal biopsy.
  • Using ESPGHAN nonbiopsy criteria (symptomatic child, TTG ≥10 ULN, positive EMA, positive HLA typing), there were four patients whose initial biopsies were not consistent with CD.  Thus these criteria identified 98.2% accurately who did not need an intestinal biopsy.  One of these four developed CD subsequently.  To achieve 100% PPV for non biopsy, the authors note that one would need an EMA titer ≥1:80.
  • Study limitations: retrospective study, lack of standardization between TTG assays

Bottomline: EMA improves the PPV of TTG testing, especially when low titer elevations are noted.  TTG alone is a highly sensitive test “with a 99.4% negative predictive value” in this study.

Related study: “Serum Anti-Tissue Transglutaminase Antibodies Detected during Febrile Illness May Not be Produced by the Intestinal Mucosa” J Pediatr 2015; 166: 761-3.  This case report describes two children with abnormal TTG (one more than 20-fold ULN)) both were EMA-negative. No mucosal anti-TTG was identified using two immunoassays.

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How to Keep Enteral Feedings Safe

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As noted previously in this blog, enteral feedings are generally safe to administer overnight (Rest easy with enteral nutrition | gutsandgrowth).  Another study (Nutr Clin Pract February 2015 vol. 30, no. 1 128-133) agrees with this finding in both open and closed systems but with the caveat that addition of modular products to enteral feeds can result in unacceptable contamination.

Here’s the abstract:

Background: Temperature is known to affect bacterial growth, but current safety recommendations for enteral formula are based on studies conducted in thermoneutral environments, which are not representative of select burn intensive care units (ICUs) that are kept therapeutically hyperthermal. This project evaluated microbial growth in 3 enteral feeding systems: closed, open, and open with modular additives (modular tube feeding [MTF]) exposed to 2 different environments. Procedures: Product for each of the 3 systems was prepared and hung in both a thermoneutral (23.3°C) and a hyperthermal (32.5°C) ICU room. At baseline, 4 hours, and 8 hours, samples were plated and incubated overnight and the number of colony-forming units (CFUs) counted. Findings: In the thermoneutral and hyperthermal environments, there was no evidence of microbial growth in the open or closed feeding systems at any time point. The MTF exhibited baseline contamination with a median of 10 CFUs (95% CI, 8–16) and significant growth over time to 54 CFUs (95% CI, 20–230) by 8 hours in the thermoneutral setting. In the hyperthermal environment, the MTF showed baseline contamination of 390 CFUs (95% CI, 40–1600) and significant growth over time, with 30% of samples exhibiting contamination levels exceeding Food and Drug Administration standards by 4 hours and CFUs being too numerous to count by 8 hours. Conclusion: CFUs in enteral formula did not differ between open and closed feeding systems in either environment for up to 8 hours; however, the addition of modulars to open systems may result in an unacceptable risk of contamination in hyperthermal environments.

Other blogs related to enteral nutrition:

Probiotics -Another Positive Study for Prevention of Necrotizing Enterocolitis

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The topic of probiotics and necrotizing enterocolitis has been discussed several times on this blog (see some links below).  Here’s an abstract from a recent J Pediatr 2015;166: 545–51.

Objective

To test the efficacy of probiotic and prebiotic, alone or combined (synbiotic), on the prevention of necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants.

Study design

A prospective, randomized, controlled trial was conducted at 5 neonatal intensive care units in Turkey. VLBW infants (n = 400) were assigned to a control group and 3 study groups that were given probiotic (Bifidobacterium lactis), prebiotic (inulin), or synbiotic (Bifidobacterium lactis plus inulin) added to breastmilk or formula for a maximum of 8 weeks before discharge or death. The primary outcome was NEC (Bell stage ≥2).

Results

The rate of NEC was lower in probiotic (2.0%) and synbiotic (4.0%) groups compared with prebiotic (12.0%) and placebo (18.0%) groups (P < .001). The times to reach full enteral feeding were faster (P < .001), the rates of clinical nosocomial sepsis were lower (P = .004), stays in the neonatal intensive care unit were shorter, (P = .002), and mortality rates were lower (P = .003) for infants receiving probiotics, prebiotics, or synbiotic than controls. The use of antenatal steroid (OR 0.5, 95% CI 0.3-0.9) and postnatal probiotic (alone or in synbiotic) (OR 0.5, 95% CI 0.2-0.8) decreased the risk of NEC, and maternal antibiotic exposure increased this risk (OR 1.9, 95% CI 1.1-3.6).

Conclusions

In VLBW infants, probiotic (Bifidobacterium lactis) and synbiotic (Bifidobacterium lactis plus inulin) but not prebiotic (inulin) alone decrease NEC.

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Preterm Neonatal Microbiota and Effect of Perinatal Antibiotics

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A recent study (Arboleya, S et al. J Pediatr 2015; 166: 538-44) provide sequential data regarding the intestinal microbiome in preterm infants in comparison to full-term infants; in addition, this study offers some insight into the changes that occur with perinatal antibiotics.

The researchers examined fecal samples at approximately 2 days of life, and then days 10, 30, and 90 in 27 preterm infants and 13 full-term babies. The study figures show the progression and changes of the microbiota over the first 90 days. In Figures 1, the profiles are the most similar between the full-term and preterm infants but there remains significant differences.

Key findings:

  • Preterm infants had higher initial percentage of Lactobacillaceae and reduced Bacteroidacease.
  • Perinatal antibiotics (including intrapartum antimicrobial prophylaxis) were noted to affect gut microbiota with increased Enterobacteriaceae organisms in these infants.

There were many confounding variables noted, including different diets, which make interpretation of the data difficult.  The full-term infants received exclusive breast milk whereas the preterm infants received mixed feedings.

A recent review (Houghteling, PD, Walker, WA.”Why Is Initial Bacterial Colonization of the Intestine Important to Infants’ and Children’s Health?” JPGN 2015; 60: 294-307) had a relevant figure:

From NASPGHAN Twitter Feed

From NASPGHAN Twitter Feed

Bottomline: Overall, Arboleya et al provide some additional baseline data but much more is needed to ascertain what factors will make children healthier –starting from before birth. The understanding of the microbiome is truly in its infancy.

Related blog posts:

 

Misdirection: False-postive Urine Cannaboid Screen due to Pantoprazole

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First of all, this post is not a joke for April 1st. But if you have a good story to tell, please feel free to comment -I’ll share a story at the bottom of this post.

A case report (Felton D et al. Pediatrics 2015; 135: 2014-16) makes a few useful points regarding testing for cannaboids in a patient admitted for cyclic vomiting syndrome.

  1. Intravenous pantoprazole could lead to a false-positive urine cannaboid screen.
  2. Cannabis hyperemesis syndrome should be included in the differential diagnosis for cyclic vomiting. (see previous blog: Think Like a Doctor -Another Reason for Cyclic Vomiting …)
  3. Don’t order every test on the differential diagnosis (my point -not the authors).

With regard to the final point, this particular case report describes a highly-impaired 13 year old with previous diagnoses of intrauterine stroke, global developmental delays, and seizures; she was nonverbal and nonambulatory.  Therefore, despite a positive urine screen, it is not surprising that the confirmatory testing for cannabis via gas chromatography-mass spectrometry was negative.

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On a side note, several years ago we had a little fun in the spirit of April 1st.  One of our neighbors had been complaining for years that they had not received ‘yard of the month’ but had lived in the neighborhood for more than 16 years. So, one year when they were out of town, we managed to borrow the ‘yard of the month’ sign, placed it in their yard, and snapped a picture.  With the collusion of a different neighbor who sends out the monthly announcement, our neighbors were informed of the recognition of their yard. It was definitely a good laugh.  At the same time, I’m a little paranoid about potential payback.

 

 

Predicting Response to Topical Steroids in Eosinophilic Esophagitis

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A recent study (Wolf WA, et al. Clin Gastroenterol Hepatol 2015; 13: 45-58) examined 221 patients in a retrospective cohort study to determine how effective topical steroids were in the treatment of eosinophilic esophagitis (EoE).  The authors studied these patients from 2006-2013; the majority received budesonide (63%) and the remainder received fluticasone; the typical dosing was 0.5 mg-1 mg twice daily and 440-880 mcg twice daily, respectively. 129 (58%) of the participants were >18 years.

Key findings:

  • 57% had histologic response with <15 eos/hpf
  • Refractory patients “were difficult to treat with dietary and second-line pharmacologic therapies, with less than half responding even after multiple second-line therapies.” The most successful second-line approach was diet: 6 of 16 (38%) had improved histology (<15 eos/hpf).  Higher doses of topical agents were effective in 2 of 14 (14%) and alternative topical agent was effective in 2 of 7 patients (29%).
  • Dilatation at the time of disease presentation (25% of the study cohort) correlated with poor clinical outcome.  Only 40% (20 of 50) had a histologic response.
  • High tissue levels of tryptase and eotaxin-3 increased the likelihood of a steroid response.

As this was a retrospective study, there were several weaknesses.

Take-home message: The findings from this large cohort show that more than 40% of patients did not have a favorable histologic response.  Some recent studies indicate that higher doses of steroids may be effective, but this may be influenced by the proportion of individuals with advanced fibrostenotic disease.

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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.

Chicago's Bean

Chicago’s Bean