Today’s AJC has a story regarding celiac disease as well as gluten sensitivity. Gluten a problem or a fad?
Related posts from this blog:
Category Archives: Nutrition
Iron and hepcidin –not just for grownups
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
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:
Pediatric NAFLD Position Paper
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?
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
Additional references:
- -JAMA 2011; 306: 206-07. State intervention in life-threatening childhood obesity.
- -Pediatrics 2009; 123: 399-406.
- –http://blog.cleveland.com/metro/2011/11/obese_cleveland_heights_child.html Commentary on this issue.
- –http://www.msnbc.msn.com/id/43727876/ns/health-health_care/t/obesity-alone-no-reason-remove-kids-their-homes/ Commentary on this issue.
Breastfeeding: protection from asthma
Good news for breastfed babies –breastfeeding may reduce risk of wheezing and asthma for several years (J Pediatr 2012; 160: 991-6).
In this prospective birth cohort study of 1105 infants from New Zealand, detailed feeding information was obtained at 3, 6, and 15 months which allowed calculation of breastfeeding duration. This information was correlated with information about wheezing and asthma collected at 2, 3, 4, 5, and 6 years.
Findings (after controlling for confounding variables):
- Each month of exclusive breastfeeding was associated with significant reductions in asthma at all timepoints. The effect was most prominent at younger ages.
- The authors estimate that if every infant in the cohort had been exclusively breastfed for 6 months, that asthma would have been reduced by 50% at 2 years, 42% at 3 years, 30% at 4 years, 42% at 5 years, and 32% at 6 years.
- In atopic children, the effects of exclusive breastfeeding are more pronounced. In this study, exclusive breastfeeding for ≥3 months reduced asthma at ages 4, 5, and 6 by 62%, 55%, and 59% respectively.
The authors note that not all studies have found that breastfeeding improves asthma. However, most of these studies reported outcomes in older children.
Related Posts:
Breastfed babies less likely to develop fatty liver
More evidence that breastfeeding improves cognitive development
Additional references:
- -NEJM 2011; 364: 701, 769. Living on a farm decreases risk of childhood asthma.
- -Thorax 2009; 64: 604-9. Breastfeeding and asthma in children followed for 8 years.
- -Br Med J 2007; 335: 815-20. Longer time of breastfeeding does not reduce allergy/asthma. n=17,046 pairs of mother-infant (13,889 followed up at age 6.5yrs)
TODAY is worrisome for a lot of tomorrows
The TODAY study (NEJM 2012; 366: 2247-56 and editorial 2315-16) =Treatment Options for Type 2 Diabetes in Adolescents and Youth.
While the study has a catchy acronym, the findings are disturbing. Eligible patients (n=699) were 10 to 17 years old were followed on average over 3.86 years; they were divided into three groups:
- Metformin 1000mg BID –48% achieved primary outcome (glycated hemoglobin <8% for at least 6 months).
- Metformin with lifestyle changes –53% achieved primary outcome. The lifestyle counseling that patients received in the study likely exceeded the typical counseling that most patients receive in clinical practice.
- Metformin with rosiglitazone (4mg BID) –61% achieved primary outcome. While this group had the best glycemic response, this group also had the greatest increase in BMI.
Other findings:
Comorbid conditions were common:
- Hypertension: at baseline in 81 (11.6%) and new cases during study 155 (22.2%)
- Dyslipidemia (LDL): at baseline in 23 (3.3%) and new cases during study 49 (7%)
- Triglyceridemia: at baseline in 127 (18.2%) and new cases during study 70 (10%)
- Microalbuminurina: at baseline in 44 (6.3%) and new cases during study 72 (10.3%)
Frequent adverse events noted with medications (Table 2 in study): gastrointestinal symptoms noted in about half of all study participants in each group, rash noted in about 40%, and elevated LFTs in about 40%.
Take home messages (borrowed from editorial):
“Most youth with type 2 diabetes will require multiple oral agents or insulin therapy within a few years after diagnosis”
“Fifty years ago, children did not avoid obesity by making healthy choices; they simply lived in an environment that provided fewer calories and included more physical activity.”
“Public-policy approaches–sufficient economic incentives to produce and purchase healthy foods and to build safe environments that require physical movement…will be necessary to stem the epidemic of type 2 diabetes and its associated morbidity.”
Related posts:
Treating diabetes with surgery
Reasons for refeeding syndrome
Refeeding syndrome (RFS) is defined as the potentially fatal shifts in fluid and electrolytes that may occur in malnourished patients who are abruptly refed either enterally or parenterally. The biochemical hallmark is hypophosphatemia. Other changes can include hypokalemia, hypomagnesemia, and thiamin deficiency. RFS can worsen the prognosis of children with celiac crisis as well (JPGN 2012; 54: 522-5).
A chart review from Lucknow, India from Jan-Dec 2010, identified 5 cases of RFS among 35 celiac patients. All were severely malnourished. All had anemia, hypoalbuminemia, hypophosphatemia, hypokalemia, and hypomagnesemia. All improved with initial caloric restriction followed by gradual escalation of caloric intake along with electrolyte supplementation.
This article shows that a variety of causes of malnutrition can lead to refeeding syndrome. Considering refeeding syndrome in any severely malnourished child may help improve the prognosis by altering the nutritional management.
Additional references:
- Nutr Clin Pract 2012; 27: 34-40. Reviewed refeeding syndrome publications since 2000. Hypophosphatemia occurred in 96% of cases (26 of 27).
- Crit Care Med 2010; 14: R172-R178. Refeeding syndrome with anorexia.
- Nutrition 2010; 26: 156-67. Review of refeeding syndrome treatment.
- Nutr Clin Pract 2008; 23: 166-71. Death due to refeeding syndrome.
- JPEN 1990: 14.1; 90-97. Refeeding syndrome review.
- Crit Care Med 1990; 18: 1030-1033. Review.
A cautionary vitamin D tale?
A recent case report indicates that pharmacologic doses of vitamin D can cause hypercalcemia and hypervitaminosis D (Pediatrics 2012; 129: e1060-63). The three cases all document good reasons for instituting therapy: craniotabes, hypocalcemic seizures, and tibial bowing. The total dose that the patients received over 7-12 weeks ranged from 112,000 IU to 168,000 IU. The ages of the patients ranged from 2 weeks to 33 months. The peak abnormal calcium for all three patients was 11 mg/dL and the peak 25-hydroxy vitamin D was 102 ng/dL. There were no clinical symptoms in these three patients due to increased calcium. A fourth oh-by-the-way patient was described as well. This patient was receiving vitamin D for an “inappropriate indication” (failure to thrive) and had received 3.6 million IU without monitoring. This led to the development of a multitude of symptoms associated with a calcium level of 17.4 mg/dL.
My take-home points:
- If giving generous doses of vitamin D, obtain a followup calcium several weeks into therapy. However, pharmacologic doses of vitamin D for valid indications pose a very low risk.
- Excessive doses of vitamin D can be detrimental. (This last statement may be akin to the warning “hot coffee might cause a burn.”)
Related blog entries:
Live longer -drink more coffee
In a previous post, I was impressed with some of the benefits of coffee (Drink Up!). More good news for coffee drinkers: drinking coffee is associated with decreased mortality (NEJM 2012; 366: 1891-1904). Full disclosure –I don’t even drink coffee & I am not being paid by industry!
This study examined a huge population, 5,148,760 person-years (1995-2008) among 229,119 men and 173,141 women in the NIH-AARP Diet and Health Study with participants aged 50-71 at baseline. With age-adjusted models, if adjusted for smoking, an inverse association between coffee consumption and mortality was noted. With 6 cups per day, the hazard ratio (HR) was 0.90 for men and 0.85 for women. For 2-3 cups, the HRs were 0.94 and 0.95 respectively.
Declines in mortality were noted for heart disease, respiratory disease, stroke, injuries/accidents, diabetes and infections, but not for deaths from cancer. However, while coffee is associated with improved mortality data, a causal role for coffee consumption in reducing mortality cannot be established with this study.
Related link:
http://www.cnn.com/2012/05/16/health/coffee-drinking-longer-life/index.html?hpt=hp_t2
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