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Identifying Biliary Atresia in Infants: New Guidelines

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S Harpavat et al. Pediatrics Pediatrics (2025) 155 (3): e2024070077. (Open Access!) Guidance for the Primary Care Provider in Identifying Infants With Biliary Atresia by 2–4 Weeks of Life: Clinical Report

Recommended Screening:

  • Office visit at 2-4 weeks of age (by 4 weeks of life)
  • Check fractionated bilirubin: If there is any pale, gray or white stools, If there is any jaundice in eyes or skin, or If there is a prior history of abnormal direct or conjugated bilirubin*
  • If direct or conjugated bilirubin is 1 mg/dL or higher, urgent consult to GI
Stool color classification

“The most important result is the initial direct or conjugated bilirubin level, which will be “high” in BA starting at birth.11,17,18 “High” is defined as exceeding the laboratory’s derived reference range, even if only by 0.1 mg/dL In the period before 2 weeks of life, “high” is not defined by exceeding a fixed cut-off or exceeding a bilirubin ratio.”

Additional Recommendations:

  • The authors indicate that followup blood testing is NOT needed if the following: 1. Any prior direct or conjugated bilirubin level that was normal (in reference range) or 2. Prior direct or conjugated bilirubin levels that were all abnormal but equivalent or decreasing over time. In this instance, equivalent or decreasing is defined as both (i) less than or equal to the initial level; and (ii) <1 mg/dL
  • “Consider adding direct or conjugated bilirubin testing when serum total bilirubin testing is performed. As mentioned earlier, many centers measure at least 1 serum total bilirubin level via heel stick or venipuncture to assess risk for bilirubin encephalopathy. Direct or conjugated bilirubin levels can be measured from the same heel stick or venipuncture sample, without needing an additional blood draw.”

My take: Any child with an elevated direct or conjugated bilirubin (above reference range) in the first two weeks of life needs to be carefully followed. This guideline also recommends using abnormal stool color and prolonged jaundice/icterus as prompting bloodwork.

In the past, it was consider normal in newborns to have elevated direct bilirubin IF there was a low ratio of direct bilirubin to total bilirubin (less than 20% in those with bilirubin >5 mg/dL). However, this can result in missed cases of biliary atresia.

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Safe Baby Formula Choices Based on Consumer Reports Testing

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From Consumer Reports, April 18, 2025: We Tested 41 Baby Formulas for Lead and Arsenic

This Consumer Reports article is likely to generate a lot of attention. Thanks to Dr. Seth Marcus for sharing this reference.

An excerpt:

While some formulas had concerning levels [of arsenic and lead], there are safer choices. After seeing our results, the FDA is pledging further action…

Consumer Reports tests in the past have found elevated levels of inorganic arsenic in fruit juice, baby food, and bottled water…Our tests found the highest inorganic arsenic level in Abbott Nutrition’s EleCare Hypoallergenic, at 19.7 parts per billion (ppb), and the second highest in Similac Alimentum at 15.1 ppb, also made by Abbott.

As we had expected, CR’s tests found lead in almost all the formulas. Lead levels ranged from 1.2 ppb to 4.2 ppb, which is below the FDA’s Closer to Zero goal, but CR’s experts believe those levels are too high...

Together the formula made by these three companies—Abbott, Mead Johnson, and Perrigo—makes up 79 percent of the U.S. market…They also said trace levels of heavy metals in the food supply are not an issue that is unique to infant formula…

Perrigo, which makes Dr. Brown’s formula and many popular store brands we tested, including Kirkland, Parent’s Choice, Member’s Mark, and Up&Up, also told us that it routinely screens its formulas for heavy metals. “These compounds and PFAS are also found in breast milk,” a spokesperson wrote. “Their levels in infant formula are insignificant and well below regulations in the United States and around the world.”

Contaminants from the environment pose a problem for our entire food supply, CR experts say. But the problem is much more urgent for formula, given how vulnerable babies who depend on it are.

The FDA has long been limited by a lack of both resources and authority to carry out all the oversight it’s tasked with. ..

Keep these test results in perspective. Environmental pollutants are pervasive in our food supply, and all the contaminants in our tests—arsenic, lead, BPA, acrylamide, and PFAS—have also been previously detected in breast milk, food, and water…

Never ever try to make your own baby formula or offer alternative foods. It’s unsafe from a nutrition standpoint…

Use clean water to mix into your powdered formula. The EPA sets limits on contaminants in tap water for most of the country, but not every part of it. If you drink water from a well, for instance, that water is not regulated by the EPA. So it’s a good idea to get well water tested for heavy metals and PFAS before using it…

“Good Choices”

  • A2 Platinum -A2 Milk Company
  • ByHeart Whole Nutrition -ByHeart
  • Happy Baby Organics -Danone
  • Kendamil Organic -Kendal Nutricare
  • Neocate Hypoallergenic -Danone
  • Parent’s Choice Infant -Perrigo
  • Similac 360 Total Care -Abbott Nutrition
  • Similac 360 Total Care Sensitive -Abbott Nutrition
  • Similac Sensitive -Abbott Nutrition
  • Similac Soy Isomil -Abbott Nutrition

“Worse Choices”

  • Dr. Brown’s SoothePro -Perrigo
  • Elecare Hypoallergenic -Abbott Nutrition
  • Enfamil Nutramagen -Mead Johnson
  • Enfamil ProSobee Simply Plant-Based -Mead Johnson
  • Kabrita Goat Milk-Based -Ausnutria
  • PurAmino Hypoallergenic -Mead Johnson
  • Similac Alimentum -Abbott Nutrition
  • Similac NeoSure -Abbott Nutrition
  • Similac Total Comfort -Abbott Nutrition
  • Up&Up (Target) Soy -Perigo

My take: Formula companies need to continue to work on minimizing all of the contaminants. Yet, if all families selected only CR’s “top choices,” there would not be enough formula for infants who are not breastfed. In addition, this problem is even more of an issue in children needing specialized hypoallergenic formulas.

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Dr. Maria Oliva-Hemker: Positioning Therapies for Pediatric Crohn’s Disease

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Recently, Dr. Maria Oliva-Hemker gave our group an excellent update on Crohn’s disease therapies.  My notes below may contain errors in transcription and in omission. Along with my notes, I have included many of her slides.

Key points:

  • Early advanced therapy results in better outcomes (see The PROFILE study results below as one example)
  • Anti-TNFs are the only therapy with a specific FDA pediatric indication. Medications can take 8-10 years after use in adults for pediatric labeling
  • IL-23 specific agents (like risankizumab) are more effective than ustekinumab that target both IL-23/IL-12
  • Recent studies show that ustekinumab is effective in children. Also, in patients who respond to ustekinumab, there is good durability
  • Infliximab is a top-line therapy in Crohn’s disease
  • Risankizumab is a top-line therapy in both biologic-naive and biologic-exposed patients with Crohn’s disease. Higher maintenance doses may capture more patients.
  • Upadacitinib is a very good therapy in patients with prior advanced therapies with either Crohn’s or ulcerative colitis. It also has a rapid onset of action (within 2 weeks)
  • Vedolizumab is less effective in those who are biologic-exposed. However, patients with predominantly colonic (UC-like) involvement may be better-suited for this therapy
  • Close monitoring and treat-to-target approaches are recommended. Usually followup scope is undertaken after one year (&/or one year after switching therapy)
  • Combination advanced therapies have shown effectiveness but it is unclear which combinations are optimal
This slide shows the Montreal Classification, an organ-based phenotype, to describe the anatomic extent and behaviors of Crohn’s disease;. The figure on the right illustrates extraintestinal manifestations of IBD. It is expected that disease classification will rely more on a molecular based approach.
The STRIDE project which defined goals of treatment was the result of consensus achieved by the International Organization of IBD. The first recommendations came out in 2015 and then these were updated in 2021 to incorporate a pediatric component.
The PROFILE study with 386 adults showed how important early effective advanced therapies. Patients receiving infliximab/azathioprine within a median of 15 days from diagnosis had remarkably better outcomes compared to step up treatment with prednisone + azathioprine.
The cytokine IL12 and IL23 shown as circles with 2 subunits attaching to their receptors share a p40 subunit (shown in red). Ustekinumab binds to that p40 subunit thereby inhibiting both the IL12 and IL23 pathways. IL23 inhibitor. Risankizumab, Mirkizumab, Guselkumab inhibit only the p19 subunit (shown in blue) and so  they only downregulate the IL-23 pathway.
Jak inhibitors targets are intracellular in location.
Pediatric data: Multicenter 2015-2020; primary outcome was CS-free remission after 1 yr. Prior to use, 50% failed 1 anti TNF and 30% 2 anti TNF. At one year, 59/101 were in steroid free remission
Upadactinib studies: Oral induction dose for UC and CD is 45 mg daily for induction
and with reduction in maintenance to 30 mg or 15 mg
Due to limited head-to-head studies, network meta analyses provides indirect evidence of comparative effectiveness. It relies on how effective a medication was compared to placebo. One of the problems with these comparisons is that there are different populations in each of these studies.
In patients who need speed to reduce symptoms, upadacitinib is favored over IL-23 agents

Though Dr. Oliva-Hemker’s lecture did not focus on ulcerative colitis, she did note that their center has recommended frequent colonoscopies (often yearly) in many of their patients with the combination of ulcerative colitis and PSC. This is due cases of colon cancer in their pediatric cohort.

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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.

Gene Therapy for Alpha-One Antitrypsin Deficiency

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An excerpt from NY Times:

Researchers have corrected a disease-causing gene mutation with a single infusion carrying a treatment that precisely targeted the errant gene.This was the first time a mutated gene has been restored to normal….

The study involved patients who have alpha-1 antitrypsin deficiency, or AATD, a genetic disease that affects an estimated 100,000 Americans…

When the nanoparticles reached the liver, the lipid layer peeled off, releasing the editor — a disabled CRISPR molecule that acted like a GPS for the genome and an enzyme to fix the mutation. The CRISPR molecule crawled along the patient’s DNA until it found the one incorrect letter that needed to be repaired among the three billion DNA letters in the genome. Then the editing enzyme replaced that letter with the correct one… Those who got the highest dose made enough normal alpha-1 antitrypsin to be in a range where no more damage should occur. 

My take: This is exciting news, though, long-term data is needed to determine if this will be a durable cure. Cost/availability will be an important consideration if effective.

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The Importance of the EARNEST Trial –Vedolizumab for Chronic Pouchitis

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V Jairath et al. Clin Gastroenterol Hepatol 2025; 23: 321-330. Open Access! Mucosal Healing With Vedolizumab in Patients With Chronic Pouchitis: EARNEST, a Randomized, Double-Blind, Placebo-Controlled Trial

Methods: EARNEST, a randomized, double-blind, placebo-controlled study, evaluated vedolizumab efficacy and safety in adults with chronic pouchitis. 

Key findings:

  • More patients treated with vedolizumab vs placebo achieved mucosal healing, reduction in ulcers and ulcerated pouch area and SES-CD remission.
Reduction in the Number of Ulcers was much better for Vedolizumab than Placebo
Proportion of patients with (A) change in ulcerated surface area
and (B) with no ulcers (ulcers >5 mm, erosions ≤5 mm)

My take: Fortunately, chronic pouchitis is uncommon in the pediatric population. This study shows that many patients with chronic pouchitis improve with vedolizumab.

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Appendectomy vs Antibiotics: The Better Choice for Pediatric Appendicitis

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Briefly noted: SD St Peter et al. The Lancet, Volume 405, Issue 10474, 233 – 240. Appendicectomy versus antibiotics for acute uncomplicated appendicitis in children: an open-label, international, multicentre, randomised, non-inferiority trial

Methods: Children (n=936) aged 5–16 years with suspected non-perforated appendicitis (based on clinical diagnosis with or without radiological diagnosis) were randomly assigned (1:1) to the antibiotic or the appendectomy group. Treatment failure: Within 1 year of random assignment, n the antibiotic group, failure was defined as removal of the appendix, and in the appendectomy group, failure was defined as a normal appendix based on pathology.

Key findings:

  • Treatment failure occurred in 153 (34%) of 452 patients in the antibiotic group, compared with 28 (7%) of 394 in the appendectomy group 
  • There were no deaths or serious adverse events in either group
  • The relative risk of having a mild-to-moderate adverse event in the antibiotic group compared with the appendectomy group was 4·3 

My take: Appendectomy was superior to antibiotic management of acute non-perforated appendicitis.

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Bamboo forest at East Palisades Trail, Chattahoochee River, Atlanta

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.

HLA-DRB1*01:03: Biomarker for Severe Ulcerative Colitis

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MV Vestergaard et al. . JAMA. Published online October 15, 2024. doi:10.1001/jama.2024.20429. HLA-DRB1*01:03 and Severe Ulcerative
Colitis

Background: This study aimed to identify biomarkers by conducting a Danish nationwide genome-wide association study (GWAS) on severe vs less severe ulcerative colitis.

Methods: Severe ulcerative colitis: Patients with severe ulcerative colitis were defined as having at least 1 major ulcerative colitis–related operation, at least 2 ulcerative colitis–related hospitalizations exceeding 2 days, and/or use of at least 5000 mg of systemic corticosteroids within 3 years of diagnosis

The authors utilized two source populations

  1. The Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT) neonatal blood spot cohort (NBS) includes individuals born in Denmark and diagnosed with ulcerative colitis from 1981 to 2022
  2. The North Denmark Biobank study is a population-based cohort of patients from Northern Denmark with inflammatory bowel disease from 1978 to 2020 (NorDIBD)

The combined cohort included 4491 patients (4153 from NBS and 338 from NorDIBD) with a mean (SD) age at diagnosis of 23.3 (8.4) years; 53% of patients were female and 27% had severe disease.

Key findings:

  • The association with HLA-DRB1*01:03 (Figure 1) had an OR of 6.38 for major operation, OR of 5.24 for at least 2 hospitalizations, and OR of 2.30 for use of at least 5000 mg
    of systemic corticosteroids in carriers vs noncarriers
  • Carriage of HLA-DRB1*01:03 allele was 2.8% in these cohorts
  • Limiation: Danish cohort -may not be applicable to other populations

My take: HLA-DRB1*01:03 is a low-frequency allele, carriers have a significantly higher risk of severe ulcerative colitis.

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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.

Why the Proposed Medicaid Cuts Matter: Children and Other Vulnerable Populations Will Suffer

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E Park. NEJM 2025; DOI: 10.1056/NEJMp2501855. Medicaid on the Chopping Block

An excerpt:

A top priority for Congress and President Donald Trump is extending and expanding tax cuts expiring at the end of 2025…Republican leaders in the House intend to make at least $880 billion in Medicaid cuts over 10 years to offset some of the tax cuts’ $4.5 trillion cost…

Medicaid, however, is more essential than it has ever been. It provides affordable, comprehensive health coverage to more than 72 million low-income Americans1…Medicaid covers about 40% of all children and births in the United States. It covers more than one third of people with disabilities and 44% of children with special health care needs…

Medicaid is especially vital for rural communities. Residents of small towns and rural areas disproportionately rely on Medicaid…

Under many of these proposals, states would face drastic reductions in federal Medicaid funding….states would have to choose among three painful options. They could dramatically raise income and sales taxes. They could deeply cut other parts of their budgets, such as budgets for K–12 education and higher education, which account for about 43% of states’ own spending. Or — the option most states would have to choose — they could slash their Medicaid programs by substantially narrowing Medicaid eligibility, restricting benefits, making it harder for eligible people to enroll in and renew coverage, and making sharp cuts to already low reimbursement rates for hospitals, physicians, and nursing homes.

As a result, many low-income children, parents, people with disabilities, older adults, and others would be at risk for becoming uninsured and forgoing needed care…As opposition becomes increasingly public, widespread, and vocal, congressional Republican leaders could ultimately view severe Medicaid cuts as too politically difficult and decide they need to drop them from budget reconciliation.

My take: This article elaborates on all the ways that Congress could curtail Medicaid spending. Ultimately, all of them will leave the states with additional costs if they are to maintain current coverage levels. Even with the proposed cuts to Medicaid, the tax cut plan is projected to add two trillion dollars each year during this administration.

Related article: 3/2/25 Patricia Murphy, AJC: Medicaid cuts from Washington would gut this Georgia pediatrician’s practice (behind paywall) “A South Atlanta pediatrician [Dr. Dorsey Norwood] says 85% of her patients are covered by government health care program…For at least one Georgia pediatrician, cutting Medicaid benefits for her young patients would leave a wound in her practice that even she couldn’t heal.”

Efficacy of Azithromycin-Metronidazole Induction in Mild-to-Moderate Pediatric Crohn’s Disease

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MT Fioretti et al. J Pediatr Gastroenterol Nutr. 2025;80:300–307. A decade of real-world clinical experience with 8-week azithromycin–metronidazole combined therapy in pediatric Crohn’s disease

Methods: This retrospective study over 10 years examined the efficacy of azithromycin-metronidazole for induction treatment in 44 children. All patients were given metronidazole (15–20 mg/kg/day two times daily, maximum of 1000 mg/day) administered daily for 8 weeks and azithromycin (7.5 mg/kg to a maximum of 500 mg/once a day) administered 5 days per week for the first 4 weeks, followed by 3 days per week for the final 4 weeks as per the initial publications.17, 18 

Key findings:

  • After 8 weeks, the overall remission rate was 64%.
  • Of the 38 patients who completed the CD AZCRO course, 28 patients (74%) entered remission (Group 1) and 10 (26%) did not (Group 2)
  • After 8 weeks, Group 1 showed improved CRP levels and higher albumin and hemoglobin levels than Group 2. Median FC declined significantly from 650 mcg/g at baseline to 190 mcg/g at Week 8 in Group 1 (p < 0.001).

The authors conclude that “a combination treatment of azithromycin and metronidazole represents an alternative induction therapy for mild to moderate pediatric CD, offering benefits in terms of cost and practicalities compared to EEN and in side effects compared to steroids.”

My take: There are a small number of children with mild Crohn’s disease who could benefit from this induction regimen. An alternative would be the use of a more modest dietary approach (eg. Mediterranean diet)

Related blog posts:

Mai Khao beach, Phuket, Thailand

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.

Antroduodenal Dysmotility in Hypermobility Disorders and Ehlers-Danlos Syndrome

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KWE Sweerts et al. Alimentary Pharmacology & Therapeutics, 2025; 61:702–705. Open Access! Analysis of Antroduodenal Motility in Patients With Hypermobility Spectrum Disorders/Hypermobile Ehlers–Danlos Syndrome

Background: Hypermobility spectrum disorders (HSD) and hypermobility Ehlers–Danlos syndrome (hEDS) are frequently associated with gastrointestinal symptoms, although the underlying mechanisms remain unclear. Since recruitment occurred before the 2017 criteria for hEDS were established, it was not possible to distinguish between HSD and hEDS. 

Methods: Retrospective review of all patients (>18 yrs) referred t for gastrointestinal motility evaluation and undergoing ADM were consecutively included from 2009 to 2023. This included 239 patients (50 HSD/hEDS and 189 non-HSD/hEDS). The HSD/hEDS group showed a lower BMI and higher use of enteral feeding than the control group (p < 0.001 and p = 0.026, respectively). This group was also younger, with a mean age of 30.4 ± 11.1 years versus 45.3 ± 15.4 years (p < 0.001).

Key findings:

  • The prevalence of antroduodenal dysmotility was not different between both groups, but enteric dysmotility was less common in the HSD/hEDS group (13% vs. 34%, p = 0.006).
  • There were similar percentages of delayed gastric emptying than non-HSD/hEDS patients; delayed gastric emptying was highly prevalent in both groups, 85% in patients with HSD/hEDS and 94% in non-HSD/hEDS patients
  • There were no differences in predominant symptoms between patients with and without HSD/hEDS.

In the discussion, the authors note that the lower rate of dysmotility combined with higher rates of enteral nutrition indicate that “factors like visceral hypersensitivity and autonomic function could be relevant in this context.”

My take: Most patients at this referral center had delayed gastric emptying. However, Ehlers-Danlos patients, in fact, had lower rates of enteric dysmotility.

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Grand Palace, Bangkok