CB Ebbeling, DS Ludwig. J Pediatr 2023; 255: 22-29. Open Access! Treatment for Childhood Obesity: Using a Biological Model to Inform Dietary Targets

This article describes the role of glycemic index and a carbohydrate-insulin model (CIM) in promoting obesity rather than the more conventional view of energy dense foods causing obesity.

• In the CIM, “dysregulation of hormonal control over fuel partitioning in response to a high-glycemic load diet leads to excess fat deposition, as an antecedent to positive energy balance…. Consuming a high-glycemic index food causes a sharp increase in blood glucose followed by a rapid decline, whereas consuming a low-glycemic index food causes a more gradual increase and decrease with a lower peak. Decreasing dietary glycemic load involves lowering carbohydrate amount and selecting sources of carbohydrate with a low glycemic index. In general, low-glycemic load foods include nonstarchy vegetables, most temperate (vs tropical) whole fruits, and legumes; and high-glycemic load foods include potato products, processed grains, sweets, fruit juices, and sugary beverages.²¹“
• “Fructose also increases fat deposition by upregulating enzymes of de novo lipogenesis via mechanisms independent of energy intake.^22,23 Thus, the conventional understanding of obesity pathogenesis (overeating causes increasing adiposity) is opposed in the CIM (increasing adiposity causes overeating).”

“Dietary targets for which there is general consensus are:

• Ample nonstarchy vegetables (eg, broccoli, lettuce), whole temperate fruits (eg, apple, orange, pear), and legumes
• No sugar-sweetened beverages
• Limited refined grains
• Adequate protein

Additional dietary targets of particular relevance to the CIM which differ to some extent from conventional recommendations include:

• Reduced amounts of starchy vegetables and total grains
• Increased healthful fats (eg, nuts, seeds, avocado, olive oil)”

” When counseling, we recommend home-prepared protein (eg, poultry, fish) over preprepared items with breading (eg, chicken nuggets, fish sticks). We do not specifically recommend reduced-fat (1% or nonfat) dairy. Emerging observational data indicate that consuming whole vs reduced-fat milk is associated with lower adiposity in children,⁶⁶…Regarding milk with added sugar and flavoring (eg, chocolate milk), prospective data indicate a direct association between consumption and adverse changes in body composition”

Three main goals with this diet approach:

1. Eat balanced meals  – Follow a Plate Model
2. Eat Paired Snacks When Hungry Between Meals
3. Stop and Think Before You Drink Sugary Beverages – Drink Water Instead

My take: I have favored the Mediterranean diet as a general goal for patients concerned with healthy eating. This article challenges the conventional approach of targeting energy dense foods in favor of avoiding high glycemic carbohydrates.

This article is a good resource–more information available at these links:

• Boston’s New Balance Foundation Obesity Prevention Center
• Boston Children’s Fit Kit Food Guide
• Paired Snacks

• M Greenhawt et al. NEJM 2023; 388: 1755-1766. Phase 3 Trial of Epicutaneous Immunotherapy in Toddlers with Peanut Allergy
• Editorial: A Togias. NEJM 2023; 388: 1814-1815. Good News for Toddlers with Peanut Allergy

Methods: This was a phase 3, multicenter, double-blind, randomized, placebo-controlled (EPITOPE) trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients (n=362) were randomized a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (250 mcg) (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. 

Key findings:

• The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group
• Treatment-related anaphylaxis occurred in 1.6% in the intervention group and none in the placebo group

Points from the editorial:

• “The primary finding is that after receiving treatment with the peanut patch for a year, 67.0% of the toddlers in the intervention group could safely ingest the peanut-protein equivalent of approximately three to four peanuts or approximately one peanut, depending on how sensitive to peanut they were at baseline. In the placebo group, 33.5% of the children reached this end point…many practitioners have been using orally delivered foods for the same purpose for approximately a decade.”
• “A trial of peanut oral immunotherapy that did not involve the use of the commercially available product was recently conducted among children 1 to 3 years of age (the Oral Immunotherapy for Induction of Tolerance and Desensitization in Peanut-Allergic Children Trial [IMPACT]).⁵…The data suggest that oral immunotherapy may have a stronger protective effect than the effect reported in the EPITOPE trial.” Able to tolerate ingestion of 10 peanuts: “In the EPITOPE trial, 37% of the children in the intervention group and 10% of those in the placebo group had this result, as compared with 71% and 2%, respectively, in the IMPACT trial.”
• ” On the other hand, epicutaneous immunotherapy appears to have a better safety profile than oral immunotherapy…For example, allergic reactions that resulted in the administration of epinephrine occurred in 10% of the children in the intervention group in the EPITOPE trial and in 22% of those in the IMPACT trial. Also, eosinophilic esophagitis was seen in 3% of the children in the IMPACT trial who had received oral peanut immunotherapy.”

My take: Immunotherapy, oral or cutaneous, can result in some tolerance to peanuts in the majority of children. However, primary prevention of peanut allergy by timely introduction of peanuts in the diet could prevent the need for this intervention. Usually, introduction is at 4-6 months of age (though with specific precautions recommended in those with severe eczema and egg allergy).

Related blog posts:

• New Strategy to Overcome Severe Reactions to Peanuts
• LEAP-ON Study: Early Peanuts Prevent Allergies
• “Separating Fact from Fiction in the Diagnosis and Management of Food Allergy”
• How Likely/Persistent is Eosinophilic Esophagitis with Peanut Oral Immunotherapy
• Peanut Allergy Prevention Guidelines
• The Peanut Story -From NEJM Blog (2015)

N Bevers et al. J Pediatr 2023; 256: 113-119. Open Access! Ferric Carboxymaltose Versus Ferrous Fumarate in Anemic Children with Inflammatory Bowel Disease: The POPEYE Randomized Controlled Clinical Trial

Methods:  Children aged 8-18 (n=64) with IBD and anemia (defined as hemoglobin [Hb] z-score < −2) were randomly assigned to a single IV dose of ferric carboxymaltose (15 mg/kg up to 750 mg) or 12 weeks of oral ferrous fumarate (9 mg/kg/day up to 600 mg in BID divided dosing). This study excluded patients with severe disease activity (eg. PUCAI >65, or PCDAI >30).

Key findings:

• One month after the start of iron therapy, the  6-minute walking distance (6MWD) z-score of patients in the IV group had increased by 0.71 compared with −0.11 in the oral group (P = .01).
• At 3- and 6-month follow-ups, no significant differences in 6MWD z-scores were observed.
• Hb z-scores gradually increased in both groups and the rate of increase was not different between groups at 1, 3, and 6 months after initiation of iron therapy (overall P = .97).
• The authors did not detect hypophosphatemia which has been described with ferric carboxymaltose

This “POPEYE” study prompted me to review how much iron is in spinach. Apparently, it is a little more than in red meat. However, red meat iron is “heme” and is better absorbed than “non-heme” iron found in spinach.

My take: In this study, more rapid improvement in 6MWD was noted in first month of treatment but there were no other significant advantages of IV iron in this group which predominantly had quiescent disease or mildly active disease; hemoglobin improvement was comparable in both groups.

Related blog posts:

• Changing Approach to Iron Deficiency Anemia in Pediatric IBD
• Anemia in IBD -NASPGHAN Position Paper
• Nutritional Anemia -Expert Review
• More Iron Infusions, Less Blood Transfusions in Kids with Inflammatory Bowel Disease; COVID-19 Transmission in Children
• Iron Injectables
• CHOP QI: Anemia in IBD Pathway

R Rosen et al. J Pediatr 2023; 256: 5-10. Airway Impedance: A Novel Diagnostic Tool to Predict Extraesophageal Airway Inflammation

Airway appearance is not a reliable marker for aerodigestive disorders. This study (n=73 completed full study) sought to use airway impedance to provide an objective measure of airway mucosal integrity.

Methods: The direct laryngoscopy was performed and videotaped for blinded scoring by 3 otolaryngologists and a specially-designed impedance catheter was placed onto the posterior larynx to obtain measurements; the impedance sensors were placed immediately below vocal cords. Following this, an endoscopy was performed and impedance measurements and biopsies were taken.

Key findings:

• Patients taking proton pump inhibitors had significantly lower mean airway impedance values (706 ± 450 Ω) than patients not taking them (1069 ± 809 Ω, P = .06).
• Patients who had evidence of aspiration on video fluoroscopic swallow studies had lower airway impedance (871 ± 615 Ω) than patients without aspiration (1247 ± 360 Ω, P = .008)

Discussion:

• Low impedance values have been correlated with esophageal inflammation. For example, in patients with active eosinophilic esophagitis impedance values of <1000 Ω are typical compared to >2500-3000 Ω in those without inflammation.
• This study suggests that low laryngeal impedance prior to EGD can provide an objective marker of laryngeal mucosal integrity. Values were lower in those with impaired swallowing/aspiration. The association with lower values in those taking PPIs may be due to ongoing GERD (acid or nonacid) and/or ongoing pepsin exposure.
• It is noted that airway impedance values were, “on average, 3-fold lower than esophageal impedance values, highlighting the differences in these microenvironments.”
• Limitations: No healthy controls

My take: Frequently, aerodigestive patients undergo extensive evaluations. This is a simple technique that could easily be added; it may be an objective marker of airway disorders “and may help reduce acid suppression use previously driven by these visual exams.”

Related blog posts:

• Incredible Review of GERD, BRUE, Aspiration, and Gastroparesis
• Good Episode of Bowel Sounds on Reflux
  Acid Suppression for Laryngomalacia -Handed This Article to My ENT Colleagues
• Something Useful for Apparent Life-Threatening Events (ALTEs)
• Blaming Reflux for BRUEs -Not Changing Despite Guideline Recommendations
• Do Acid Blockers Given to Infants Increase the Risk of Allergic Disease?
• 2018 Pediatric Gastroesophageal Reflux Clinical Practice Guidelines
• Clinical evaluation not sensitive for aspiration
• How Many Kids with Reflux have Reflux?
• Better to do a coin toss than an ENT exam to determine reflux

J Sabella et al. JPGN 2023; 76: 282-287. Multidisciplinary Tiered Care Is Effective for Children and Adolescents With Rumination Syndrome

The was a retrospective single-center study (n=171). The median length of treatment was 6.5 months for outpatient care, four days for intensive outpatient care and nine days for intensive inpatient care.

Key findings:

• After treatment, 72% of OP, 95% of IOP, and 96% of IP patients reported that symptoms were better or fully resolved compared to baseline
• In a subset of 16 children, At follow-up (median 5.3 months), 86% of IOP and 66% of IP patients had symptoms that remained better or resolved.
• The authors found “an association between patient or family reluctance to accept the diagnosis of rumination syndrome and a lack of response to treatment. Prior studies have demonstrated the importance of commitment and belief in the process of treatment and/or fully commit to the behavioral treatment process as a barrier to care.”

In a commentary on this article from Pediatrics Nationwide, Dr. Peter Lu noted: “What was striking to me was how effective the intensive treatment programs are. Both of those groups included the most severe of patients, oftentimes, they’ll have a feeding tube or a central line for parenteral nutrition. Even in that selected, very severe refractory group, we had very good response rates to treatment…RS is a disorder that cannot be effectively treated by a GI doctor alone…Treatment of RS involves a GI doctor and a GI psychologist, and we oftentimes will involve one of our GI dieticians”

My take: This study shows that treatment can be very effective in treating rumination syndrome, especially if the patient/family is amenable to therapy.

Related blog posts:

• The Half Empty Glass: Rumination Outcomes
• Internet Survey: Lots of People Have Rumination
• Expert Advice for Diagnosis and Treatment of Rumination Syndrome
• Baclofen for Rumination
• Dupixent for Eosinophilic Esophagitis (1-11 yrs) and Clinical Diagnosis of Rumination from DDW Tweets

Also, good tips on managing rumination were given on a bowel sounds podcast: Desale Yacob & Ashley Kroon Van Diest – Rumination Syndrome (August 2021)

K Tazi et al. JPGN Reports 4(2):p e316, May 2023. | DOI: 10.1097/PG9.0000000000000316. Open Access: Complications of Percutaneous and Surgical Gastrostomy Placements in Children: a Single-Centre Series.

In this retrospective single-center pediatric (n=124) study, the authors analyzed complications that occurred up to 1 year after placement. Key findings:

• Fifty-nine patients (47.6%) underwent endoscopic placement, 59 (47.6%) surgical placement, and 6 (4.8%) laparoscopic-assisted percutaneous endoscopic gastrostomy. 
• 29 (14.4%) major and 173 (85.6%) minor complications were reported
• This study highlights at least 1 complication (regardless of severity) in 106 (85.5%) patients and reports a significantly lower complication rate in the PEG group (major and minor combined) compared to the surgical group (laparoscopy and laparotomy) (OR, 0.3; 95% CI, 0.07–0.9) (P = 0.001).
• In the endoscopic group, patients with concomitant neurological disease had significantly more early complications (25.8 vs. 3.6%; OR, 9.1)
• In the surgical group, patients with undernutrition had significantly more major complications (12.1% vs. 40%; OR, 4.7; 95% CI, 1.2–18; P = 0.01)

Discussion:

• The authors note that although their results found fewer complications in the PEG group, other studies have reported lower complications in surgically-placed GTs. “Baker et al (⁴)^. report, like Sanderg et al (⁹)., an advantage of the laparoscopic technique compared to the endoscopy technique in terms of major complication (OR, 0.29; 95% CI, 0.17–0.51; P = 0.0001). Several other studies (^9,20,21) show similar results.”
• “Although a single prophylactic antibiotic therapy with cefazolin is systematically administered before each procedure, the rate of infectious complications remains high: 13 cases of abdominal wall abscess or cellulitis (6.4% of total complications) and 33 cases of minor infection (16.3% of total complications) requiring local treatment.”
• The strengths of this study are an exhaustive collection of detailed data permitting a precise analysis of complications

My take: The majority of studies suggest that laparoscopic GT placement is safer, unlike this study. A more definitive answer would require a randomized prospective study with rigorously-collected data. Also, GT complications are common, ~85% in this study; thus, family education is important both before and after GT placement.

Related blog posts:

• Gastrostomy Tube Recommendations in Pediatrics
•  Is a Laparoscopic Gastrostomy Better Than a Percutaneous Endoscopic Gastrostomy?
• Updated ESPGHAN Percutaneous Endoscopic Gastrostomy Position Paper
• Helpful Position Paper: Percutaneous Endoscopic Gastrostomy in Children
• Complications with G-tube Placement (reports 2015 study with same group)
• Which kids who aspirate need a gastrostomy tube?
• Long-term Outcomes with Pediatric PEG Placement

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