Adverse Childhood Experiences Increase Anxiety and Disorders of Gut-Brain Interaction

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J Fritz et al. J Pediatr Gastroenterol Nutr. 2025;80:100–107. The relationship between adverse childhood experiences and disorders of the gut–brain interaction

Methods: Retrospective review of patients aged 3–18 years with ACE scores documented between October 1, 2019 and April 30, 2022. from two large primary care medical groups in Southern Maine within the MaineHealth system. ACE screening tool was taken at a routine WCC at a primary care office. From these patients, we identified from the medical record whether patients were referred to a general pediatric GI clinic in Southern Maine. 

Key findings:

  • Four hundred and one (44.7%) were diagnosed with a DGBI.
  • With each additional adverse experience, patients were 1.09 times more likely to have a DGBI diagnosis (p ≤ 0.001). An anxiety diagnosis mediated 73% of this relationship (p = 0.012).

Limitations:

There are many limitations to this study. The vast majority of patients with DGBIs were likely never referred to a pediatric GI clinic. While anxiety was found to mediate the relationship between ACEs and DGBIs, perhaps an alternative explanation was that anxiety increased the likelihood of GI referral. In addition, the authors note that” patients who are perceived as anxious by their gastroenterologist are more likely to receive a DGBI diagnosis.27 The nature of a symptom-based diagnosis for DGBI was also a limitation as not all patients had sufficient documentation to apply Rome criteria for inclusion.”

My take: Despite the limitations of this study, it appears that ACEs are associated with DGBIs mediated mainly by anxiety.

Related blog posts:

From Manuel Antonio Park
View from Manuel Antonio

Understanding Patient-Specific Blood Count Setpoints

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BH Foy et al. Nature (2024). https://doi.org/10.1038/s41586-024-08264-5. Haematological setpoints are a stable and patient-specific deep phenotype

Background: The complete blood count (CBC) is an important screening tool for healthy adults and a common test at periodic exams. However, results are usually interpreted relative to one-size-fits-all reference intervals1,2, undermining the precision medicine goal to tailor care for patients on the basis of their unique characteristics3,4.

Key findings:

  • Routine CBC indices fluctuate around stable values or setpoints5, and setpoints are patient-specific, with the typical healthy adult’s nine CBC setpoints distinguishable as a group from those of 98% of other healthy adults, and setpoint differences persist for at least 20 years.
  • Setpoints also define patient-specific reference intervals and personalize the interpretation of subsequent test results. In retrospective analysis, setpoints improved sensitivity and specificity for evaluation of some common conditions including diabetes, kidney disease, thyroid dysfunction, iron deficiency and myeloproliferative neoplasms

This study is discussed by Eric Topol: Your Lab Tests. “This [individualized setpoints] enabled the ability to differentiate increased risk of progression to Type 2 diabetes in people as a function of MCHC setpoint, likelihood of hypothyroid status (elevated thyroid stimulating hormone (TSH) from the current MCV, low iron storage (ferritin) from the drop in hemoglobin, and even a mutation in Janus Kinase (JAK2) in people with high platelet setpoints (>9-fold higher rate of mutations, which are associated with several blood cancers.).”

My take: This study indicates that for each individual there past test results are more useful than establised normative values. Deviation from a person’s setpoint, even if in the normal range, is more indicative of development of a medical problem. However, this type of data is not always utilized. This study focused on CBC values, but there may be setpoints with other common labs as well; more studies are needed.

Position Paper: Pediatric Refractory Constipation Management

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AL Kilgore et al. JPGN 2024; https://doi.org/10.1002/jpn3.12390. Open Access! Evaluation and management of pediatric refractory constipation: Recommendations from the NASPGHAN neurogastroenterology and motility committee

Selected Recommendations:

Evaluations:

  • Screen for thyroid disease and celiac disease (though acknowledges that the data regarding an association between celiac disease and constipation are inconsistent)
  • The use of an AXR in RC should be reserved for those patients unable to provide a reliable medical history and/or unable to allow for a physical exam (including a DRE), or to evaluate for mechanical obstruction or colonic distention when considering surgical interventions
  • A contrast enema (CE) can be used to screen for HD or to assess colorectal anatomy
  • There is no evidence to recommend the routine use of defecography in children
  • Abdominal ultrasound has a good agreement with digital rectal exam (DRE) to evaluate for fecal impaction but should not be performed in place of DRE
  • ARM should be used to screen for the presence of a RAIR. If anal spasms and prolonged sphincter relaxation are detected during ARM, an assessment for spinal abnormalities can be considered
  • An LS MRI should be performed in pediatric patients with RC associated with physical or neurological signs of spinal anomalies, signs of neurogenic bladder on urodynamics, or when the anorectal manometry (ARM) is abnormal suggesting spinal cord abnormalities
  • Colonic transit time (CTT) via radiopaque markers should be completed for patients with RC with equivocal medical history and to screen for the need to perform colonic manometry (CM)
  • Colonic manometry (CM) should be performed only after medical therapy has been exhausted and surgical therapy is being considered. CM should be used to guide the timing and type of surgery to address RC. CM should be used to guide when to perform an ostomy takedown
  • Rectal biopsies should not be used routinely in patients with RC and are indicated exclusively in patients with a suspected diagnosis of HD

Pharmaceuticals:

  • High-dose sennoside (or Bisacodyl) is a mainstay of management of RC and should be optimized for the individual patient before considering further management options
  • A secretagogue (or prucalopride) should be considered as an adjunct to a high-dose stimulant laxative when treating RC with poor response to optimized high-dose stimulant laxatives or when high-dose stimulant laxatives are not tolerated
  • There is no clear role of anal botox in the treatment of patients with RC without a diagnosis of IAS achalasia
  • Early intervention with daily stimulant laxatives in the treatment of FC is encouraged to try to prevent the disease progression from functional constipation (FC) to RC
  • Antegrade and Retrograde Treatments:
Routine dosages of frequently used antegrade and retrograde solutions and additives
  • The last part of the recommendations include antegrade continence enemas, surgical approaches, and complicated algorithms (see Figure 1 and Figure 2)

My take: These recommendations address a widespread problem for pediatric gastroenterologists and are useful for those with and without an interest in motility disorders.

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  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.

ESPGHAN Guidelines for PSC in Children

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PF van Rheenen et al. JPGN 2024; DOI: 10.1002/jpn3.12378. Open Access! Primary sclerosing cholangitis in children with inflammatory bowel disease: An ESPGHAN position paper from the Hepatology Committee and the IBD Porto group

Recommendations:

  • In children with suspected or confirmed IBD, screening for liver disease is usually performed at 3 to 6 months intervals and a work‐up for underlying liver disease is most commonly initiated when liver enzymes exceed 2x the upper limit of normal
  • Use MRCP as the radiological modality of choice for diagnosing PSC
  • Consider performing a liver biopsy in children with IBD and suspected PSC in the following circumstances: i) Normal biliary tree at MRCP, ii) raised immunoglobulin G and the presence of liver-specific autoantibodies, or iii) clinical uncertainty before steroid induction therapy for IBD
  • Perform fecal calprotectin screening at least once yearly in children with isolated PSC and/or AIH to select patients for diagnostic endoscopy for suspected inflammatory bowel disease (panel recommends cutoff of >150 indicating need for ileocolonoscopy)
  • Surveillance colonoscopy should be considered in children with PSC–IBD and the following risk factors of colorectal cancer: i) persistent active colonic inflammation, ii) longstanding colitis (≥8 years), or iii)  a family history of colorectal cancer in a first-degree relative <50 years. (The overall risk of colon cancer in those <18 yrs of age is very low)
  • UDCA may be prescribed at doses of 15–20 mg/kg/day. Despite evidence of improvement of liver enzymes, its long-term effect on disease progression has not been demonstrated. Consider a 6-months therapeutic trial of UDCA, either immediately after PSC diagnosis or when spontaneous normalization of GGT does not occur in the first 6 months postdiagnosis. Continue UDCA treatment if there is a meaningful reduction or normalization of GGT or improvement of symptoms
  • Oral vancomycin may be prescribed for a potential improvement in liver biochemistry as well as bowel inflammation. Its long-term effect on disease progression has not been demonstrated
  • In children with PSC–IBD and biochemical, serological, and histological features of AIH, the use of corticosteroids and antimetabolites may suppress immune-mediated hepatitis. In the absence of convincing AIH features, the use of corticosteroids and antimetabolites is not indicated to manage PSC
  • Children with PSC, relevant bile-duct strictures and cholestatic symptoms should be assessed for liver transplantation. When their symptoms are likely to improve following biliary intervention, ERCP can be considered
  • Recommended blood testing for children with PSC: At diagnosis: Autoantibodies (ANA, anti-SMA, anti-LKM-1, anti-LC1, and anti-SLA), Every 3-6 months: ALT, AST, GGT, Albumin, INR, Platelets, CRP. Every 12 months: IgG, AFP, and Fat Soluble vitamins. Consider f/u autoantibodies in those with elevated IgG at f/u lab testing

My take: This is a useful position paper; it does not have a zillion recommendations like some other ESPGHAN positions papers. Given the frequency of liver enzyme elevation in patients with IBD, mild to modest elevations may need to be observed before launching an extensive evaluation (see related blog posts below).

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How Triglycerides Affect Outcomes in Pediatric Pancreatitis

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ZM Sellers et al. J Pediatr 2025; 276: 114298. Impact of Elevated Serum Triglycerides on Children with Acute Recurrent or Chronic Pancreatitis from INSPPIRE-2

Using the INSPPIRE-2 cohort of children with acute recurrent or chronic pancreatitis (CP) (n = 559), the authors compared the outcomes for children based on their triglyceride levels. Definitions: normal triglycerides (<150 mg/dL), any high triglycerides (HTG) (≥150 mg/dL, mild-moderate HTG (150-499 mg/dL), moderate HTG (500-999 mg/dL), and severe HTG groups (≥1000 mg/dL).

  • Key findings:
    HTG was not associated with an increase in the number of pancreatitis attacks per person-years
  • HTG was not associated with an increase in CP prevalence
  • HTG severity was associated with increased pancreatic inflammation, pancreatic cysts, pain, hospital days, number of hospitalizations, intensive care, and missed school days
  • Interestingly, there were less pancreas gene variants in the severe HTG group which supports the notion that HTG can be a driver of pancreatitis disease

Discussion:

  • “It is well-established that severe HTG levels increase pancreatitis risk by increasing serum chylomicrons and free fatty acids, causing pancreatic ischemia, acidosis and vascular injury…In adults, TG levels >/= 200 mg/dL are independently associated with pancreatic necrosis.”

My take: Checking triglyceride levels, which is in accordance with NASPGHAN recommendations, is a good idea. HTG is a potentially-modifiable risk factor for more severe disease. Levels that substantially increase the pancreatitis severity (500 or higher) merit treatment even in the absence of pancreatitis

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Optimizing Fluid Resuscitation in Pediatric Acute Pancreatitis

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N Norris et al. J Pediatr 2025; 276: 114329. Liberal Fluid Resuscitation is Associated with Improved Outcomes in Pediatric Acute Pancreatitis

This single-center retrospective study with 227 patients (2013-2023) examined the role of liberal fluid administration/type of fluid administration and outcomes in children with acute pancreatitis. Overall, 100 patients received normal saline (NS) and 41 received lactated ringers (LR). Liberal fluid management was considered to be >1.5x the maintenance.

Key findings:

  • Patients who received liberal fluids were less likely to be admitted or transferred to the intensive care unit compared with those receiving conservative management (OR, 0.32)
  • The liberal NS fluid group with early feeding had the lower rates of moderate/severe manifestations of AP compared with other combinations of diet and fluid orders except the conservative LR group
  • Moderate/severe AP was highest in the conservative NS group (14/37 [38%]), followed by liberal LR (6/31 [19%]), liberal NS (9/63 [14%]); it was lowest in conservative LR group (0/10 [0%]).

In the discussion, the authors note that adult studies have supported a more moderate approach to IVFs (1.5 mL/kg/hr) given the risks of fluid overload in WATERFALL trial.

My take:

  1. It is surprising that so few patients received LR in this study; there has been some evidence that LR is better than NS for AP since 2014 (see blog posts below)
  2. Especially in those receiving NS, more liberal use of IVFs appears beneficial. Reasonable to start at 1.5 x maintenance (as recommended by Dr. Freeman)
  3. Though children generally tolerate liberal IVFs better than adults due to better cardiovascular function, a prospective randomized study is needed to determine which fluid strategy is optimal.
  4. Early enteral feeding is beneficial in most cases
View from the Rialto Bridge, courtesy of Steven Liu who has some amazing pictures

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Key Advances in 2024: An Overview from GutsandGrowth (Part 4)

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This year I had the opportunity to give a lecture to our group that reviewed much of the important advances that happened in 2024. Here are some of the slides (if you have any trouble reading the slides, you can search for the original blog post using author name).

Key Advances in 2024: An Overview from GutsandGrowth (Part 3)

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This year I had the opportunity to give a lecture to our group that reviewed much of the important advances that happened in 2024. Here are some of the slides (if you have any trouble reading the slides, you can search for the original blog post using author name).

Key Advances in 2024: An Overview from GutsandGrowth (Part 2)

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This year I had the opportunity to give a lecture to our group that reviewed much of the important advances that happened in 2024. Here are some of the slides (if you have any trouble reading the slides, you can search for the original blog post using author name).