Category Archives: Nutrition

Optimizing lipids to minimize cholestasis

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As discussed in previous blog entries (PNAC, PNALD, and IFAC, More on PNAC, Four advances for intestinal failure), the right amount of lipid and the type of lipid both can contribute to parenteral nutrition associated cholestasis (PNAC).  More information about SMOFlipid which is a complex mixed-type lipid emulsion derived from soybean, coconut, olive, and fish oils is available (JPGN 2012; 54: 797-802).  SMOF contains 30% soybean oil, 30% MCT, 25% monounsaturated fatty acids, and 15% fish oil.

This study had a retrospective cohort comparison design & examined serum bilirubin over 6 months in children with PN-associated cholestasis (PNAC).  In one cohort, 8 patients received the SMOFlipid and the other 9 patients continued on Intralipid (IL).

The SMOF cohort was receiving 81% of caloric needs as PN at entry whereas the IL cohort was receiving 92%.  Six months later, SMOF cohort was receiving 68% of caloric needs as PN compared with 50% for IL cohort.  Nevertheless, the SMOF group had improved cholestasis with a median bilirubin drop of 99 μmol/L compared with an increase of 79 μmol/L among IL patients.  Overall, 5 of 8 children in the SMOF group had resolution of jaundice compared with 2 of 9 in the IL group.

While the authors state that SMOF may have important properties to prevent PNALD, the study has limited ability to draw any firm conclusions.

The authors state that no other treatment innovations were introduced; however, the authors overlook the large discrepancy in lipid volume administered.  The IL group was receiving much more lipid both before and during study.  Prior to entry of study, the IL group was receiving about 3.1 g/kg/day whereas the SMOF group about 2 g/kg/day; the SMOF group continued initially at the same lipid dosing with the new formulation.  This is one of the problems with historical controls.  While the authors might believe that the cholestasis improved because of the lipid content, the key factor may in fact be the amount of lipid given.

In the same issue (JPGN 2012; 54: 803-11), specific plant sterols (PS) were elevated among neonates with intestinal failure-associated liver disease (IFALD).  This study looked at 28 neonates and 11 children from Finland who required PN for more than 28 days.  Specific markedly-elevated PS included stigmasterol, sitosterol, avenasterol and campesterol (Table 4 in study).  Some of these PS in the neonates were more than 20-fold higher than healthy controls.

Keep it cool

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Now, what cooler than being cool?
Ice cold!
I can’t hear ya! I say what’s, what’s cooler than being cool?
Ice cold!
Alright alright alright alright alright alright alright alright alright alright alright alright alright alright alright alright!

Lyrics for “Hey Ya!” by Outkast

Keeping it cold is also the advice if you want to keep the bactericidal activity of breastmilk intake (JPGN 2012; 55: 146-49).  This study examined the effects of freezing from 48 healthy donors who provided samples of fresh breastmilk.  Bactericidal activity was determined by thawing breastmilk (in duplicate) and innoculating with bacterial strains and then comparing growth in breastmilk compared with control samples.

Freezing at -20 degrees celsius (C) for 1 month did not effect the bactericidal activity of breastmilk against either E coli or P aeruginosa.  In contrast, when samples were stored for three months, freezing at -80 degrees C was protective of this activity whereas -20 degrees C was not.

So if you are storing breastmilk for longer than 1 month, keep it cold if you can.

Related blog entry:

Long-chain polyunsaturated fatty acids, breastmilk, and infant cognition

Cholesterol controversy

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Recent guidelines (Pediatrics 2012; 130: 353-56) have recommended universal screening for hypercholesterolemia between ages 9-11 along with additional targeted screening.  These recommendations have been met with a number of criticisms (Pediatrics 2012; 130: 349-52).

In the first referenced commentary, the experts who issued the guidelines commissioned by the National Heart Lung and Blood Institute (NHBLI) claim that the criticism “misrepresent the evidence regarding screening and the specificity and rigor of the guideline development.”  In the second commentary, the guidelines are considered overly aggressive and not adequately founded on evidence-based medicine.  In addition, they cite two JAMA commentaries that also question the wisdom of the guidelines (JAMA 2012; 307: 257-58, & 259-60).

NHBLI recommendations:

▪  Universal screening of all 9-11 year-olds with a nonfasting lipid panel.

▪  Targeted screening of 2-8 year-olds and 12-16 year-olds with 2 fasting lipid profiles.  The targeted group are for those with diabetes, hypertension, BMI >95%, smoke cigarettes, have a parent with cholesterol >240 (or known dyslipidemia), 1st or 2nd degree relative (includes parents, aunts, uncles, and grandparents) with stroke or coronary artery disease <55 years for men or <65 for women.  According to the critical commentary, 30-40% of children will meet family history criteria and many more will meet other criteria.

▪  If LDL ≥130 mg/dL, then a “CHILD-1” diet is recommended.

▪  Individuals with abnormal screening are to have fasting lipid panels every 6-12 months indefinitely even if their values become acceptable.

Criticisms and responses by guideline authors in italics

▪  While the critics concede that cumulative exposure to high LDL and hypertension increase the risk of cardiovascular disease (CVD), they indicate that with the exception of a small number of individuals (rare homozygous familial hypercholesterolemia) that there is not proof that intervention in childhood is necessary.  The chain of evidence cited by the panel has “notably the absence of even observational evidence or modeling to estimate the clinical event benefits of screening for and intervening on these risk factors in children.”  Atherosclerosis is a lifelong process…Heterozygous familial hypercholesterolemia affects 1:500 and 51% of untreated men develop CV disease events by age 50 years… Accidental death studies (ages 15-30 years) have shown that a 30 mg/dL increase in non-HDL was equivalent to 2 years of vascular aging.  Bogalusa Heart Study showed that number of risk factors correlated with increased atherosclerosis at autopsy after accidental death.  Carotid intima media thickness in adulthood correlates with LDL levels obtained between 12-18 years of age.

▪  No quantification of potential harms such as neuroses, family conflict, CVD anxiety or from medication.  Among children with familial cardiovascular disease, interview studies have shown positive future health perceptions and effective coping.  ‘A study of universal CV risk screening in schools, accompanied by environmental change, showed improvements in healthy lifestyle behaviors and CV risk profiles.’  Risk of statin therapy, (only 0.8% of adolescents would be eligible per authors) has shown no adverse effects in children and adolescents.

▪ The majority of the panel members…disclosed an extensive assortment of financial relationships with companies making lipid-lowering drugs and lipid-testing instruments.  Evidence regarding the efficacy and safety of these medications would not be available without academic partnership with industry.  Potential conflicts of interest were declared and vetted.

▪  Cost/cost-effectiveness. The present policy proposes an intervention applied to a healthy and asymptomatic population, with an enormous impact on costs and the potential to transform well children into patients with a chronic disease label. “Any intervention with nonzero benefit may be recommended, regardless of how much it costs and how much better health might be achieved by investing those resources elsewhere.”  There have been several studies exploring the cost-effectiveness of screening and management strategies for familial hypercholesterolemia (FH). In the Netherlands, a genetic screening program showed that new cases of FH gained 3.3 years of life at an average lifetime cost of US$8700 per year gained.  More complex cost-effectiveness modeling of treatment of children and adolescents has not yet been performed.

So who is right in this debate?

Previous related blog entry:

Cardiovascular disease for the entire family

Weight of the Nation

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A perspective article, NEJM 2012; 367: 389-391, addresses the topic of whether Americans are ready to solve the problem of obesity.  Short answer: No!

The article discusses the Institute of Medicine (IOM) report “Accelerating Progress in Obesity Prevention: Solving the Weight of the Nation” along with the accompanying HBO documentary (HBO: The Weight of the Nation).

“The centerpiece of THE WEIGHT OF THE NATION campaign is the four-part documentary series, each featuring case studies, interviews with our nation’s leading experts, and individuals and their families struggling with obesity. The first film, CONSEQUENCES, examines the scope of the obesity epidemic and explores the serious health consequences of being overweight or obese. The second, CHOICES, offers viewers the skinny on fat, revealing what science has shown about how to lose weight, maintain weight loss and prevent weight gain. The third, CHILDREN IN CRISIS, documents the damage obesity is doing to our nation’s children. Through individual stories, this film describes how the strong forces at work in our society are causing children to consume too many calories and expend too little energy; tackling subjects from school lunches to the decline of physical education, the demise of school recess and the marketing of unhealthy food to children. The fourth film, CHALLENGES, examines the major driving forces causing the obesity epidemic, including agriculture, economics, evolutionary biology, food marketing, racial and socioeconomic disparities, physical inactivity, American food culture, and the strong influence of the food and beverage industry.”

While the IOM report identifies a need for structural changes in our environment, public opinion consistently focuses on personal responsibility.

  • 64% identify overeating, lack of exercise, and watching too much TV as the biggest causes
  • 18% identify external factors as the biggest causes, including exposure to junk food, lack of safe places to play, limited availability of healthy foods

Obstacles for addressing this problem also include the following:

  • Obesity-prevention efforts may further stigmatize individuals. The article specifically cites criticism aimed at ‘ads that aired in Georgia;’ these were pulled after concerns of increasing obesity stigma.
  • “Issue-attention cycle” problem.  “This pattern occurs when initial public alarm over the discovery of a problem and optimism about its quick resolution are replaced by the realization that solving the problem will require some public sacrifice and will displace powerful societal interests.”

Related blog posts:

Is obesity neglect?

NAFLD Guidelines 2012

Treating diabetes with surgery

Lower leptin with physical activity

Staggering cost of obesity

Iron and hepcidin –not just for grownups

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As alluded to in a previous post (Help with hepcidin), hepcidin is integral to iron metabolism.  In a recent study (J Pediatr 2012; 160: 949-53), serum and urine hepcidin concentrations in preterm infants were found to correlate well with iron homeostasis markers in preterm infants.

This study examined 31 preterm infants (23-32 weeks gestational age).

Findings:

  • Serum hepcidin was highest in infants with systemic inflammation.
  • Both serum and urine hepcidin correlated strongly with ferritin (Figure 2 in study) and negatively with soluble transferrin receptor/ferritin-ratio.
  • Infants with lower hemoglobin concentrations and higher reticulocyte counts had lower serum hepcidin.
  • There was good correlation between urine and serum hepcidin (Figure 1 in study). As such, urine hepcidin may become useful non-invasive marker for iron status in sick preterm infants

Long-chain polyunsaturated fatty acids, breastmilk, and infant cognition

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A lot has been written about improving infant cognition and breastfeeding, even on this blog (More evidence that breastfeeding improves cognitive development).  Formula companies in their efforts to duplicate the nutritional value of breast milk have supplemented with a number of agents, including long-chain polyunsaturated fatty acids (LCPUFA).  But, does this work?

A meta-analysis of LCPUFA supplementation failed to show any significant effect on early infant cognition (Pediatrics 2012; 129: 1141-49).  Twelve trials with 1802 infants met inclusion criteria.  Included trials were randomized clinical studies that measured cognition with Bayley Scales of Infant Development.

LCPUFAs have been hypothesized to be a potential reason for improved cognition.  LCPUFAs are vital for cell membranes and play a critical role in development and growth.  The two main LCPUFAs are docosahexaenoic acid (DHA) and arachidonic acid (AHA). “An estimated 30-fold increase in the amount of DHA and AA in the infant forebrain occurs between the last trimester of pregnancy and the first 2 years of life.”

The authors note that while breastfed babies tend to have higher intelligence, confounding factors have made it difficult to determine whether actual nutritional differences in breast milk are the reason for this difference.  On average, breastfeeding mothers have higher intelligence, larger incomes, and spend more time with their infants.  Thus, bonding/social interactions as well as other breast milk properties (eg antimicrobial, antiinflammatory, and immunomodulatory) may be important factors.

On the same subject, a second article in the same issue (Pediatrics 2012; 129: 1134-40) also showed that breastfed infants had slightly improved cognitive development compared with formula-fed babies (both cow’s milk and soy formula).  This conclusion was based on Bayley Scales of Infant Development and the Preschool Language Scale-3.  In total, this study examined 391 infants at ages 3, 6, 9, and 12 months.  The authors state that “models were used while adjusting for socioeconomic status, mother’s age and IQ, gestational age, gender, birth weight, head circumference, race, age, and diet history”  –that’s a lot of variables to adjust!

More on breast milk from previous blog entries:

Breastfed babies less likely to develop fatty liver

Breastfeeding: protection from asthma

Pediatric NAFLD Position Paper

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A previous blog post (NAFLD Guidelines 2012) described comprehensive, up-to-date NAFLD guidelines from AASLD, AGA, and ACG.   Another group of experts from ESPGHAN (European Society for Pediatric Gastroenterology, Hepatology, and Nutrition) has also published a position paper on the diagnosis of NAFLD in children; coincidentally, these were published recently as well (JPGN 2012; 54: 700-13).

While there is some overlap in the information between the two guidelines, there are some notable differences.  The JPGN manuscript does include a nice differential diagnosis list  which can cause fatty liver disease (Table 2), including some rare entities like Dorfman-Chanarin syndrome, Cantu syndrome, Madelung lipomatosis, and numerous medications.  This review has more emphasis on etiology.

Table 3 lists a recommended workup in children with suspected NAFLD:

  • Standard liver function tests/blood counts/coagulation studies
  • Fasting glucose & insulin
  • Lipid profile
  • Glucose tolerance test & glycosylated hemoglobin
  • Calculation of HOMA-IR, markers of insulin resistance

AND Tests to exclude other liver diseases: 

  • Lactate, uric acid, iron, ferritin, pyruvate
  • Copper, ceruloplasmin, 24-hour urinary copper
  • Sweat test
  • Celiac serology (TTG IgA and serum IgA)
  • α-1-antitrypsin levels and phenotype when indicated
  • Amino and organic acids
  • Plasma free fatty acids and acyl carnitine profile
  • Urinary steroid metabolites
  • Other specific tests as suggested by evaluation (eg. viral hepatitis panel, serum immunoglobulins, liver autoantibodies)

When one looks at the recommended diagnostic algorithm (Figure 1) and tests outlined, these guidelines are not nearly as practical as the NAFLD guidelines from AASLD, AGA, and ACG and often contradictory between the tables/figures and the text.  How much would it cost for the recommended testing if/when extrapolated to the vast numbers of individuals with these disorders?  In addition, a much more limited diagnostic approach is suggested in the final section than outlined in Table 3 and Figure 1.

Imaging: these authors advocate LFTs and ultrasonography in all obese children (> 3 years) and adolescents.  If normal LFTS and sonography, the algorithm suggests the use of MRI if clinical signs of insulin resistance.  Later, the authors conclude “MRI is not cost-effective.”

Liver Biopsy: while the authors state that there is “no present consensus or evidence base to formulate guidelines” for liver biopsy, this is not well-reflected in their diagnostic algorithm in which arrows point to liver biopsy in almost everyone –either early liver biopsy or eventual biopsy in patients with persistent disease.  Accepted liver biopsy indications, according to the executive summary, include the following:

  • Exclude other treatable disease
  • Suspected advanced disease
  • Before pharmaceutical/surgical treatment
  • Research purposes

My conclusion about this position paper is it is less helpful than the AASLD/AGA/ACG guidelines.  In fact, when extensive diagnostic testing is recommended by experts, it is fortunate that other expert guidelines are available that support a more cost-effective approach.  In NAFLD cases that seem atypical and especially in the very young patient, this reference may still be helpful.

Is obesity neglect?

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Usually not –according to a thoughtful commentary on this controversial topic (J Pediatr 2012; 160: 898-99).

Suggested criteria for child removal:

  • 1. High likelihood for serious and imminent harm
  • 2. Reasonable likelihood that coercive intervention will be effective
  • 3. Absence of alternative options for addressing the problem

However, “allowing a child to lose all opportunity to live into healthy adulthood when effective treatment is available runs contrary to the central mission of child rearing…When this occurs, regardless of the cause, it must be all about the child, and something must be done.”

Related blog posts:

Treating diabetes with surgery

Lower leptin with physical activity

Staggering cost of obesity

Additional references: