Category Archives: Pediatric Gastroenterology Intestinal Disorder

How Accurate is Serology at Predicting Mucosal Healing in Pediatric Celiac Disease?

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A recent study (Am J Gastroenterol doi: 10.1038/ajg.2014.200) shows that in children, unlike adults, that normalization of celiac disease (CD) serology correlates well with mucosal healing.

In this study, 150 children with biopsy-proven CD were prospectively evaluated with duodenal biopsies, tissue transglutaminase (tTG) IgA serology, and deamidated gliadin peptide (DPG) IgG serology.  After maintaining a gluten-free diet (GFD) for at least 1 year, participants underwent followup evaluation.

  • Of the 97 with normalization of their serology, 91 had normal biopsies (Marsh 0) and 6 had slight abnormalities (Marsh 1).
  • Of the 27 with positive serology, only 6 had Marsh 3 changes.
  • Overall, 124 (82.7%) had normalization of duodenal mucosal biopsies irregardless of serology.

Higher rates of mucosal healing are possible with longer duration of GFD.

On the other hand, a recent retrospective study (JPGN 2014; 59: 229-31) notes that among 40 children who underwent followup endoscopic evaluation (>4 months after GFD, median 24 months), most of whom were symptomatic, only 25 had complete healing. Though among those with adherence to a GFD, only five had persistent villous atrophy (Marsh 3 lesion) . Serological correlation was not provided.

Take-home message: Followup biopsies are not needed in children with normalization of their serology (tTG IgA and DGP IgG).  That is, serology correlates well with mucosal healing in children with celiac disease on a GFD >12 months. However, it is certainly reasonable to consider followup endoscopy in those who are symptomatic, especially if serology is abnormal.
In a related matter, the new requirements regarding gluten-free labeling have been implemented -here’s a link from the LA Times: Celiac Regulations or First federal gluten–free regulation takes effect

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  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.

Nutrient Deficiencies with Celiac Disease

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A recent study (JPGN 2014; 59: 225-28) examined fat-soluble vitamin deficiencies in pediatric patients with newly diagonosed Celiac disease (CD).

Of the 83 patients analyzed between 1995-2012 at the Mayo clinic, the key findings:

  • No patients had vitamin A deficiency
  • Two patients had vitamin E deficiency.  Both of these patients had complete villous atrophy along with a malabsorptive presentation.
  • Nine patients had mild-to-moderate vitamin D deficiency (less than the reported frequency in the general pediatric population)
  • All of these vitamin deficiencies corrected with gluten-free diet and vitamin supplements.

A limitation of the study was a selection bias as not all children underwent vitamin level measurements.

Take-home message (from authors): “fat-soluble deficiencies are uncommon in children with a new diagnosis of CD.  Routine measuring of fat-soluble vitamin levels may not be necessary.”

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One More Way to Prevent CVL Infections

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While a recent study (JPGN 2014; 59: 177-81) discusses the results of several strategies for limiting CVL infections, I found one approach in particular of interest.

This single center study (2009-2013, n=48 children) from Birmingham, UK examined a multidisciplinary enhanced care pathway regarding CVL care.  Implementation of this pathway lowered the risk of all-cause line infections from 1.98 per 1000 parenteral nutrition days to 0.45.  The pathway included training care providers, careful discharge planning, having those with skin conditions see dermatologists, and monitoring compliance.

One important observation was that methicillin-sensitive Staphylococcus aureus (MSSA) infections were often preceded by local signs of infection for a short period prior to systemic infection.  “We devised a pathway for exit site infections in which a swab is taken and empiric topical mupirocin commenced immediately. A decision on any further management is made after 24 to 48 hours.”

Take-home message: Implementing a CVL care pathway lowers CVL infections.  Implementing topical therapy at the first signs of a localized infection can be an important part of this effort.

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Magnetic Foreign Bodies –Still a Problem

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After reading a recent article on swallowed magnetic foreign bodies (J Pediatr 2014; 165: 332-35), I was thinking quite tangentially about an article from The Onion a few years ago: Falling Down Laundry Chute And Breaking Neck Remains America .‘s No. 548,221 Killer.  In this Onion article, the author sarcastically bemoans the attitude that many people adopt that “this could never happen to me.”

What this Journal of Pediatrics study adds to the literature is that swallowed magnetic foreign bodies remain a significant health threat and are likely to remain that way despite recent recalls.

Key finding: 94 pediatric patients were identified at this single center as having infested magnetic foreign bodies between 2002-2012, with increasing incidence in the last three years of the study period.  The median age was 4.5 years. Six patients required surgical removal.

Bottomline: Magnet ingestions are a much more serious health threat than falling down a laundry chute.

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Costs versus Quality

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So I can return to our radiology department without cowering, I wanted to elaborate on this morning’s post.  My focus for this morning’s blog was on cost transparency.  What our pediatric radiologists emphasized to me is that quality is another key issue for patients.  Everyday at our institution there are numerous CT scans, MRIs and xrays that are reviewed from outside institutions.  Many of these studies were performed poorly and may not be interpretable = “total crap.”  And, many of these studies were unnecessary to begin with.

A couple pointers:

  • Open MRIs usually produce lousy images.  They are mainly suitable for individuals too large to fit in conventional MRIs.
  • MRI quality is dependent on high strength magnets.  A minimal of 1.5 Tesla magnet, but preferably a 3 Tesla magnet, will produce better images.
  • It is not just the radiologist that matters.  If radiology techs are not certified/accomplished, then imaging results suffer.  Techs may not focus CT scanners properly and produce a much wider field of radiation then is necessary.
  • CT scans need to minimize radiation while producing good images.  Most children’s hospitals have adopted protocols to assure that this takes place.

Radiological tests are often a ‘black box’ for families –they have no idea what is really going on.  A CT scan/MRI at low quality place may be akin to a cold hamburger at a fast food restaurant whereas a study at a high quality institution may be more similar to the best steak in town.  In addition, the quality of the images can truly be life altering.  This is likely more of an issue in pediatrics than in adult medicine.

Bottomline: In our quest for price transparency, we also need to make sure we are truly comparing apples to apples.  Highlighting value of a particular study and quality are equally important.

If any radiologists reading this post have more pointers, please comment.

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Why Adding Vitamin D May Not Help IBD

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Despite all of the accolades that vitamin D has received, the fact that low vitamin D is associated with worse outcomes, in a number of disease states, does not prove causality. A recent article indicates that vitamin D is likely more of a marker of disease activity than a mediator of disease activity in inflammatory bowel disease (IBD), and specifically Crohn’s disease (CD) (Inflamm Bowel Dis 2014; 20: 856-60).

Background: Binding sites for the vitamin D receptor (VDR) have been “identified in genes associated with CD, and vitamin D has been shown to enhance the production of interleukin-10 (IL-10) and induction of regulatory T-cells.”

Design:The authors prospectively collected samples of 37 CD patients; the mean age in those with active disease (n=20) was 34 years and it was 30 years in those with inactive disease. In 8 patients with active disease, vitamin D levels were measured at the time of active inflammation (day 0) and at 14 days after receiving infliximab (day 14).

  • Key finding in these 8 patients: Vitamin D (25-OH) was 23 ng/mL on day 0 and 40 ng/mL 2 weeks later.  Only 1 of these 8 patients was taking a vitamin D supplement.
  • Key finding in the entire cohort: in the active disease group mean vitamin D level was 27 ng/mL compared with 38 ng/mL in those in remission (P=0.02).

Take-home point: There is an inverse relationship between vitamin D levels and disease activity.  However, the early increases in vitamin D levels with clinical response to anti-TNF therapy suggests that a major mechanism of vitamin D deficiency is related to the burden of systemic inflammation.  Hence, repeat testing when patients are in remission may obviate the need for vitamin D supplementation in many patients.

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Will This Change ALTE-GERD Practice?

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This blog has highlighted several publications which have shown the lack of benefit and potential harm of pharmaceutical agents for gastroesophageal reflux “disease” (GERD) in infancy (see links below). However, in current practice, proton pump inhibitors and histamine receptor antagonists are used frequently.  Now, another influential study (J Pediatr 2014; 165: 250-5) has shown the lack of GERD as a causal mechanism in acute life-threatening events (ALTEs) and demonstrated other pathophysiologic mechanisms. However, changing physicians’ practice in this regard may prove to be as difficult as avoiding overprescribing antibiotics, or convincing reluctant parents to vaccinate their children.

So what did this study show?

This study of 20 infants (10 with proven ALTE and 10 healthy controls) had pharyngoesophageal manometry.  Key findings:

  • Infants with ALTE (vs controls) had delays in restoring aerodigestive normalcy (P=.03).  This was indicated by more frequent and prolonged spontaneous respiratory events (SREs)
  • Infants with ALTE had a lower magnitude of protective upper esophageal sphincter contractile reflexes (P=.01)
  • Infants with ALTE had swallowing as the most frequent esophageal event associated with SREs (84%), a higher proportion of failed esophageal propagation (10% vs 0%, P=.02), an more frequent mixed apnea mechanisms (P=<.01) along with gasping breaths (P=.04)

The associated editorial (pg 225-26) explains some of the limitations of the study, including the fact that the patients had a mean gestational age of 28 weeks.

The authors conclusion: “In infants with ALTE, prolonged SREs are associated with ineffective esophageal motility ,,,suggestive of dysfunctional regulation of swallow-respiratory junction interactions.  Hence, treatment should not target gastroesophageal reflux, but rather the proximal aerodigestive tract.”

Take-home message: (from the editorial): “Far too many low birth weight (and term) infants are being unnecessarily treated with a variety of antireflux medications that have serious side effects and few, if any, demonstrable benefits.”

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Enteral Fish Oil and Intestinal Adaptation in Premature Infants

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A provocative article (J Pediatr 2014; 165: 274-9) examines supplementation of enteral fat/fish oil in premature infants as a mechanism to reduce parenteral nutrition associated cholestasis (PNAC).  While the study’s limitations will prevent any dramatic conclusions, the article and associated editorial (pgs 226-27) do make several useful points.

Before discussing the limitations, the design of the study:

Infants were block randomized (block size of 8) into either a control group or treatment group.  While both groups received conventional PN, the treatment group received supplemental enteral fat as microlipid and fish oil after tolerating enteral feeds at 20 mL/kg/d.  Microlipid was started at 1 g/kg/d and advanced up to 2.5 g/kg/d; coinciding with microlipid increases, parenteral intralipid was decreased.  Fish oil was started at 0.2 g every 12 hours and was advanced to a maximum of 0.5 g every 6 hours.  The two fish oil products were Major Fish Oil 500 (Major Pharmaceuticals) and Rugby Sea Omega 50 (Rugby Laboratories).

The limitations include the following:

  • Small cohort of 18 patients in each arm
  • Due to the smell of fish oil, the study could not truly be blinded which introduces potential bias
  • Only 7 of the 36 patients could be considered to have short bowel syndrome as most of the infants had small amounts of intestine resected
  • Advancement of enteral feedings were halted if stoma output reached 20 mL/kg/d.  The editorialists note that 40 mL/kg/d would be more typical.  Thus, in both the treatment group and the control group, there was significant opportunity to reduce PN by more aggressive enteral nutrition advancement.

With these limitations in mind, there authors were able to show that supplemental fat (with fish oil) was associated with less parenteral intravenous lipid, and reduced conjugated bilirubin prior to anastomosis.  However, there was no significant difference in PN duration.  Growth parameters were similar prior to anastomosis, but improved in the treatment group after anastomosis.

In the editorial, it is noted that “enteral feeding with a high-fat diet has been demonstrated to enhance structural features of resection-associated adaptation, the underlying mechanisms for this phenomenon are still presently unknown.”

Take-home message: Enteral fat/fish oil supplementation helped decrease parenteral intravenous lipids in this study.  More broadly, advancing enteral nutrition by accepting higher ostomy outputs is likely the best strategy to avoid PNAC and other PN-associated complications.

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Probiotics for NEC -More Work is Needed (part 2)

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For very low birth weight (VLBW) premature infants, there is even more evidence that probiotics are effective (The Journal of Pediatrics Volume 165, Issue 2 , Pages 285-289.e1, August 2014 -thanks to Kipp Ellsworth for abstract link).

Abstract ():

Study design

Within the observational period (September 1, 2010, until December 31, 2012, n = 5351 infants) study centers were categorized into 3 groups based on their choice of Lactobacillus acidophilus/Bifidobacterium infantis use: (1) no prophylactic use (12 centers); (2 a/b) change of strategy nonuser to user during observational period (13 centers); and (3) use before start of observation (21 centers). 

Results

The use of probiotics was associated with a reduced risk for necrotizing enterocolitis surgery (group 1 vs group 3: 4.2 vs 2.6%,P = .028; change of strategy: 6.2 vs 4.0%, P < .001), any abdominal surgery, and hospital mortality. Infants treated with probiotics had improved weight gain/day, and probiotics had no effect on the risk of blood-culture confirmed sepsis. In a multivariable logistic regression analysis, probiotics were protective for necrotizing enterocolitis surgery (OR 0.58, 95% CI 0.37-0.91; P = .017), any abdominal surgery (OR 0.7, 95% CI 0.51-0.95; P = .02), and the combined outcome abdominal surgery and/or death (OR 0.43; 95% CI 0.33-0.56; P < .001).

Probiotics For NEC -More Work is Needed (part 1)

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From Kipp Ellsworth’s Twitter Feed:

The Time for a Confirmatory NEC Probiotic Prevention Trial in ELBW Infants is Now. Editorial in J Peds  (The Journal of Pediatrics
Volume 165, Issue 2 , Pages 389-394, August 2014)

This editorial reviews previous studies and recommends implementing a Probiotic Trial in North America. Here’s an excerpt:

“An adequately powered double-blinded placebo-controlled trial replicating a previous effective NEC prevention study in VLBW infants was published (the ProPrem trial)…the study revealed a significant reduction of NEC: from 4.4%-2.0% but no effect on mortality (4.9% vs 5.1%)…A closer look at the results of the ProPrem study, however, reveals that the probiotic supplementation did not have any effect on NEC in the ELBW (<1000 g) infants, which is consistent with two small previous studies reporting data on these infants separately.36, 42 Thus, there is currently no compelling evidence for recommending prophylactic probiotics to prevent NEC in infants with a birth weight <1000 g. Especially important is the lack of safety information in these most immature and highly vulnerable babies…Probiotics appear promising for use as prevention strategy for NEC, but there is still insufficient data for general recommendation of the use of probiotics in the ELBW infant. We argue, therefore, that now is the time to conduct in the North American setting, a high quality confirmative NEC prevention trial using probiotics in at-risk ELBW infants.”

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