A recent study (C Belza et al. JPEN 2019; https://doi.org/10.1002/jpen.1692) showed that SMOFlipid reduced the frequency of cholestasis in intestinal failure patients. Thanks to Kipp Ellsworth for reference.
An Observational Study of Smoflipid vs Intralipid on the Evolution of Intestinal Failure–Associated Liver Disease in Infants With Intestinal Failure. From Abstract:
This was a retrospective cohort study of infants with IF with a minimum follow‐up of 12 months in 2008–2016. Patients were stratified into 2 groups: group 1 received SMOFlipid; group 2 was a historical cohort who received Intralipid. The primary outcome was liver function evaluated using conjugated bilirubin (CB) levels…
Thirty‐seven patients were evaluated (17 = SMOFlipid, 20 = Intralipid). SMOFlipid patients were less likely to reach CB of 34 (24% vs 55%, P = 0.05), 50 µmol/L (11.8% vs 45%; P = 0.028), and did not require Omegaven (0% vs 30%; P = 0.014). CB level at 3 months after initiation of parenteral nutrition (PN) was lower in patients receiving SMOFlipid (0 vs 36 µmol/L; P = 0.01). Weight z‐scores were improved for patients receiving SMOFlipid at 3 months (−0.932 vs −2.092; P = 0.028) and 6 months (−0.633 vs −1.614; P = 0.018).
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Crater Lake, OR
A recent study (C Binder et al. J Pediatr 2019; 211: 46-53) examined electrophysiological brain maturation in a randomized double-blinded controlled trial of SMOF lipid compared to soybean lipid emulsion for extremely low birth weight (ELBW) premature infants. This was a prespecified secondary outcome analysis of a randomized trial of 230 infants (2012-2015).
It is recognized that the ELBW infants have very little nutritional reserve. In addition, DHA which is transferred to the fetus in high amounts in the last trimester is absent from parenteral soybean lipid emulsions. Thus, the authors explored whether SMOF lipid which is a mixture of lipids (30% soybean oil, 30% medium-chain triglycerides, 25% olive oil, and 15% fish oil) and contains DHA would have a favorable effect on neurocognitive outcomes.
In this study, the authors examined amplitude-integrated electroencephalography measurements (aEEG) to assess neurodevelopment. Both groups received similar lipid dosing, SMOF 2.2 g/day and Soybean 2.1 g/day.
- Among the available 121 infants in the subgroup with aEEG (n=63 SMOF, n=58 soybean), maximum maturational scores on aEEG were achieved 2 weeks earlier in the SMOF group (36.4 weeks vs 38.4 weeks, P<.001).
- aEEG is a marker of neurocognitive development; however, more adequate outcomes of neurodevelopmental progress are needed. The authors plan to follow these infants up to 5 years of age.
My take: This study is very favorable for the use of SMOF lipids in premature infants. — SMOF lipid emulsion by itself may improve neurocognitive outcomes. In addition, clinicians are more likely to provide adequate amounts of lipid calories with SMOF as compared to soybean emulsion which is often restricted to minimize liver injury. Giving adequate lipid calories is also likely to enhance neurological outcomes.
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Incredibly blue waters of Crater Lake, Oregon -from Wizard Island
A recent double-blind randomized study (A Repa et al. J Pediatr 2018; 194: 87-93) compared a mixed lipid emulsion (SMOFlipid) to a soybean-oil lipid in 223 extremely low birth weight infants. Median time on parenteral nutrition was ~23 days.
- The primary outcome of parenteral nutrition associated cholestasis (PNAC) was NOT significantly different in the two groups: 10.1% for SMOF and 15.9% for control group (P=.20).
- No other outcome measures were affected, including ROP, BPD and growth.
The authors note that even the control group had less cholestasis than previous cohorts and indicated that the use of probiotics and possibly more aggressive enteral feeds were at work.
My take (borrowed in part from authors): These results “cannot be generalized to infants with substantially longer time on PN.” However, this study shows that SMOFlipid alone will not prevent cholestasis, which is well-known to be multifactorial.
This blog entry has abbreviated/summarized this presentation. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.
Improvement in GGT Predicts Event-free Survival in Primary Sclerosing Cholangitis Regardless of Ursodeoxycholic Acic Treatment.
Mark Deneau et al. (Grand Watkins Prize).
- PSC is difficult to study due to its rarity and due to its slow progression; thus surrogate biomarkers are needed.
- Alkaline phosphatase is not a good biomarker in children
- GGT level at one year after diagnosis was predictive of prognosis
- Ursodeoxycholic acid does not appear to be effective
Optimizing Nutrition in Intestinal Failure
Justine Turner, University of Alberta
- Human milk is an ideal “formula” for infants, including those with intestinal failure
- Oral feedings are important
- Combination of bolus feeds and continuous feeds is reasonable
- SMOFlipid allows higher lipid dose administration without hepatoxicity; this may improve cognitive outcomes
- Amino acid based formulas have higher osmolality which can contribute to diarrhea
Patients with >50% of small bowel and >50% of colon were most likely to achieve enteral autonomy (GIFT registry)
This blog entry has abbreviated/summarized these presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.
Here is a link to postgraduate course syllabus: NASPGHAN PG Syllabus – 2017
Biliary Atresia: Update on diagnostic and prognostic biomarkers and therapeutic interventions
Cara Mack Children’s Hospital of Colorado
- 84% of biliary atresia is isolated; 16% are syndromic with other defects
- Direct bilirubin is (mildly) elevated at birth in patients with biliary atresia
- Total bilirubin 3 months after Kasai predicts outcome. If <2 mg/dL, then unlikely to need a transplant in the first 2 years of life.
- Reviewed biomarkers including Th1, Autotaxin, IL-8
- Nutritional support. Better nutrition improves outcomes after liver transplantation.
- Fat soluble vitamin supplementation
- Cholangitis prevention. Some studies have shown that prophylactic antibiotics may reduce incidence of cholangitis.
- No therapeutic interventions that delay progression of this disease
CHILDREN Cohort Mgt of Vitamin Supplementation
Steroids are not helpful after Kasai procedure
Diagnosis and Management of Pediatric NAFLD 2017
Stavra Xanthokos Cincinnati Children’s Hospital Medical Center
- NAFLD is #2 cause of liver transplantation in adults and on its way to becoming #1
- ALT is still the best screening tool; NASPGHAN guidelines recommends screening overweight/obese children 9-11 years of age
- Ultrasound has poor sensitivity and specificity for NAFLD; it is helpful for detecting gallbladder disease
- Bariatric surgery has been effective for NAFLD
SMOFlipid and the Pediatric Patient
Peter Wales Hospital for Sick Children (Toronto)
Slides are not available in syllabus
- Improving outcomes noted in the intestinal failure population
- Dr. Wales reviewed proposed improvements with Omega-3 lipids -less cholestasis, less hepatitis, and less fibrosis
- Compared improvements with lipid minimization (1 g/kg/day) compared to newer agents: omegaven and SMOFlipid. Additional studies are needed due to limitations of previous studies
- Discussed SMOFlipid vs. Intralipid trial at 5 centers in Canada. N=24.
- At SickKids: SMOFlipid for all preterms at admission & for term infants after 2 weeks of PN. Dosing 2-2.5 g/kg & now accounts for 85% of lipid usage at institution
- None of the lipid products were designed for preterm infants. Intralipid has a pediatric indication and other products are used off label
- Lipid restriction probably affects brain size/development; thus, a lipid agent that allows for higher doses likely will be beneficial for developmental outcomes. The retina can be used as a biomarker of the brain affects of lipids.
Painful Chronic Pancreatitis: Management/therapeutic interventions
Vikesh Singh Johns Hopkins University School of Medicine
Slides are not available in syllabus
Briefly noted: M Sorrell et al. JPGN 2017; 64: 783-88. In this small study with 13 infants (mean gestational age of 28 weeks) who had short bowel syndrome or severe dysmotility and direct bilirubin ≥4 mg/dL (mean 9.8 at enrollment), patients received a fish oil-based lipid emulsion (1 g/kg/d). They were compared with 119 GA-matched controls.
Overall, the authors found the fish oil supplement to be safe. All patients had resolution of cholestasis. They note the difficulty of proving effectiveness and performing studies in this population. “Neonatologists…find themselves faced with …a growing body of uncontrolled data that suggests benefits of an unapproved treatment…An attempt to perform a randomized controlled comparison of a plant-based lipid emulsion to FishLE in preventing PNALD in infants at risk was terminated early after an interim analysis revealed much lower than expected incidence of PNALD…[making] trials ethically problematic.”
My take: The data remain incomplete and make it difficult to use a therapy like Omegaven that is quite expensive (not covered) and not FDA approved. The availability of SMOFlipid is likely to result in less usage of plant-based soy products.
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