More breastmilk, better development

A recent study further explored breastmilk’s effect on infant cognitive and motor development in the French EDEN Mother-Child Cohort Study (J Pediatr 2013; 163: 36-42).

The authors acknowledge that previous studies have shown that breastfed children have  higher scores at tests on cognitive abilities; “however, some authors suggested that these results were due to the difference between the socio-demographic and occupational characteristics of mothers who breastfed and those who did not.”  Though, a large randomized trial (Arch Gen Psychiatry 2008; 65: 578-84) showed convincing data that a  longer duration of exclusive-breastfeeding duration improved children’s cognitive development.

So why did the authors bother with this study? The authors note that few studies have been performed in France where breastfeeding is less common than other European countries and their object of showing a dose-response relationship would further the arguments for causality.

Design: 1387 two-year-olds and 1199 three-year-old children were assessed from the EDEN cohort (2002 pregnancies) which prospectively collected data at birth, 4 months, 8 months,   1 year, and 2 years.

Results:

  • After adjusting for many confounding factors, infants who had breastfed scored 3.7 points higher on the Communicative Development Inventory (CDI) than infants who had never breastfed.
  • Longer breastfeeding duration was associated with better cognitive and motor development in 2- and 3-year-old children.  Each additional month of breastfeeding was associated with an increase of 0.75 CDI points and 1.00 in the Ages and Stages Questionnaire (ASQ).

Take-home message: Most studies, including the present, have shown benefits of breastfeeding on infant development.  In addition, there is likely a dose-response relationship.

Related blog posts:

Elevated Celiac Serology Associated with Reduced Infant Birth Weights

Using a population-based study of 7046 singleton pregnancies (from the Netherlands), the authors of a recent study have shown an inverse relationship between levels of anti-tissue transglutaminase IgA (TTG) antibodies and fetal growth (Gastroenterol 2013; 144: 726-35).

Results:

  • Newborns of positive TTG (>6 U/mL) weighed 159 g less at birth than newborns of mothers who tested negative for TTG.  In addition, newborns with mothers who had intermediate TTG levels ( 0.8 U/mL to 6 U/mL) had growth restriction of 53 g.
  • Among the intermediate TTG group, the results were more pronounced (2-fold greater) in those carrying the HLA risk molecules for celiac disease.
  • These birth weight changes were not associated with maternal nutritional status or deficiencies related to hemoglobin, iron, folate, or vitamin B12 deficiency.
  • Gestational age was not affected by TTG titers.

In the discussion, the authors note that other studies have shown that undiagnosed celiac disease increases the risk for intrauterine growth retardation; this risk can be eliminated by treating celiac disease.  The latter is a risk factor for lower neuropsychological performance.  This study was the first that took into effect the different TTG titers and correlated with additional nutritional parameters.

The authors speculate that celiac disease could have direct effects on the placenta.  In addition, other nutritional parameters could play a role such as vitamin D and calcium which were not included in this study.  Another important consideration is that celiac disease can result in increased miscarriages.  As a result, the “true” effect on newborn growth may be underestimated due to a “survivor bias.”

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Could antibiotics make you fat?

Studies in mice have shown that those exposed to antibiotics had higher total fat mass/body fat without additional weight gain.  In addition, a study of infants indicated that early antibiotic exposure may also be a risk factor for increased weight gain.

From Gastroenterology and Endoscopy News, June 2013: http://www.gastroendonews.com/ViewArticle.aspx?d=In%2bthe%2bNews&d_id=187&i=June+2013&i_id=961&a_id=23385

“Ilseung Cho, MD, MS, assistant professor of medicine, associate program director, Division of Gastroenterology, NYU School of Medicine, New York City, said, “Many investigators who study the gut microbiome think that it plays a significant role in the obesity epidemic in concert with a variety of other risk factors, such as poor dietary habits or a sedentary lifestyle. The microbiome plays a key role in a variety of host functions, including immune response and metabolism.”

Effect of Antibiotics

Dr. Cho was the lead investigator on a study in mice that demonstrated that antibiotics altered the gut microbiome in such a way as to affect murine metabolism and cause increased adiposity (Cho I et al. Nature 2012;488:621-626). Investigators administered subtherapeutic doses of penicillin, vancomycin, penicillin plus vancomycin, or chlortetracycline to young mice in their drinking water; a control group received no antibiotics. There were 10 mice per group. After an exposure period of seven weeks, the mice did not differ significantly in weight gain, but all four antibiotic-exposed groups had significantly higher total fat mass (P<0.05) compared with controls, and most (with the exception of the vancomycin group) had higher percent body fat (P<0.05).

The antibiotic exposure caused taxonomic changes in the microbiome, with the ratio of the phylum firmicutes to the phylum Bacteroidetes elevated in the antibiotic-exposed mice. Additionally, there was evidence of metabolic changes. For example, glucose-dependent insulinotropic polypeptide was elevated in the antibiotic-exposed mice, and glucose tolerance tests showed a trend toward hyperglycemia.

“In our paper, we describe a model where, by exposing mice to low-dose antibiotics, we were able to alter their microbiome,” said Dr. Cho. “Altering their microbiome resulted in a metabolic change in the mice that led to increased adiposity. The paper demonstrates that we are able to affect host metabolism by altering the gut microbiome.”

Around the same time that Dr. Cho and his colleagues published their results, a related paper about antibiotic exposure in infants was published in advance online (Trasande L et al. Int J Obes 2012 Aug 21 [Epub ahead of print]).

“Knowledge of the importance of the microbiome in human development raises new issues about antibiotic use in children, as such exposures may disrupt the microbial ecology,” the authors wrote.

In the longitudinal birth cohort study, investigators analyzed data from 11,532 children. Exposure to antibiotics during three early-life time periods (ages <6 months, 6-14 months, 15-23 months) was assessed by questionnaires that had been administered to the parents near the measured time interval. Body mass indices (BMIs) were examined at five time points (six weeks, 10 months, 20 months, 38 months and seven years).

Exposure to antibiotics during the period before 6 months of age—and only during that period, of those studied—was consistently associated with increases in BMI from 10 to 38 months. At 38 months, children who had been exposed to antibiotics before 6 months had significantly higher standardized BMI scores (P=0.009) and were 22% more likely to be overweight than children who had not been exposed (P=0.029). The researchers controlled for known social and behavioral risk factors for obesity.”

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The Pediatric Nutrionist Blog

One of my colleagues, Kipp Ellsworth, at Children’s Healthcare of Atlanta has started a pediatric nutrition blog: 

The Pediatric Nutritionist | Covering the world of infant, child … (www.childrensnutrition.org)

The site contains:

  • Core lectures section containing several presentations addressing the basics of pediatric nutrition
  • Feature Articles (long-form articles covering expansive clinical nutrition topics)
  • Protocol Development (articles covering institutional efforts to develop nutrition support protocols for various populations)
  • Journal Club
  • Clinical Vignettes (short-form articles or discussions on issues facing  clinical practice)

I’ve reviewed the site and I think it will be a useful resource for pediatric gastroenterology providers as well as general pediatricians.  Kipp has had a twitter feed which has provided links to a large number of nutrition articles and this site is likely to be a helpful extension.  Already on the site, there are a few powerpoint lectures; the one on formulas for infants and children provides a particularly good overview.

Live longer -don’t take your vitamins?

A recent editorial by Paul Offit provides data that taking more vitamins than your daily requirement is more likely to increase your risk of cancer and death (this has been noted on this blog as well –see related links below).

Link: nyti.ms/1bhK2Eg 

Here is an excerpt:

last year, a Cochrane review found that “beta carotene and vitamin E seem to increase mortality, and so may higher doses of vitamin A.”

What explains this connection between supplemental vitamins and increased rates of cancer and mortality? The key word is antioxidants.

Antioxidation vs. oxidation has been billed as a contest between good and evil. It takes place in cellular organelles called mitochondria, where the body converts food to energy — a process that requires oxygen (oxidation). One consequence of oxidation is the generation of atomic scavengers called free radicals (evil). Free radicals can damage DNA, cell membranes and the lining of arteries; not surprisingly, they’ve been linked to aging, cancer and heart disease.

To neutralize free radicals, the body makes antioxidants (good). Antioxidants can also be found in fruits and vegetables, specifically in selenium, beta carotene and vitamins A, C and E. Some studies have shown that people who eat more fruits and vegetables have a lower incidence of cancer and heart disease and live longer. The logic is obvious. If fruits and vegetables contain antioxidants, and people who eat fruits and vegetables are healthier, then people who take supplemental antioxidants should also be healthier. It hasn’t worked out that way.

The likely explanation is that free radicals aren’t as evil as advertised. (In fact, people need them to kill bacteria and eliminate new cancer cells.) And when people take large doses of antioxidants in the form of supplemental vitamins, the balance between free radical production and destruction might tip too much in one direction, causing an unnatural state where the immune system is less able to kill harmful invaders. Researchers call this the antioxidant paradox.

In December 1972, concerned that people were consuming larger and larger quantities of vitamins, the F.D.A. announced a plan to regulate vitamin supplements containing more than 150 percent of the recommended daily allowance. Vitamin makers would now have to prove that these “megavitamins” were safe before selling them. Not surprisingly, the vitamin industry saw this as a threat, and set out to destroy the bill. In the end, it did far more than that.

Industry executives recruited William Proxmire, a Democratic senator from Wisconsin, to introduce a bill preventing the F.D.A. from regulating megavitamins. On Aug. 14, 1974, the hearing began.

Speaking in support of F.D.A. regulation was Marsha Cohen, a lawyer with the Consumers Union. Setting eight cantaloupes in front of her, she said, “You would need to eat eight cantaloupes — a good source of vitamin C — to take in barely 1,000 milligrams of vitamin C. But just these two little pills, easy to swallow, contain the same amount.” She warned that if the legislation passed, “one tablet would contain as much vitamin C as all of these cantaloupes, or even twice, thrice or 20 times that amount. And there would be no protective satiety level.” Ms. Cohen was pointing out the industry’s Achilles’ heel: ingesting large quantities of vitamins is unnatural, the opposite of what manufacturers were promoting.

A little more than a month later, Mr. Proxmire’s bill passed by a vote of 81 to 10. In 1976, it became law. Decades later, Peter Barton Hutt, chief counsel to the F.D.A., wrote that “it was the most humiliating defeat” in the agency’s history.

As a result, consumers don’t know that taking megavitamins could increase their risk of cancer and heart disease and shorten their lives; they don’t know that they have been suffering too much of a good thing for too long.

Paul A. Offit is the chief of the infectious diseases division of the Children’s Hospital of Philadelphia and the author of the forthcoming book “Do You Believe in Magic?: The Sense and Nonsense of Alternative Medicine.”

Related blog entries:

Celiac disease and less diabetes?

While there is a well-recognized association between Celiac disease and insulin-dependent diabetes mellitus (IDDM), a recent study shows a lower prevalence of non-insulin dependent diabetes mellitus (NIDDM) and metabolic syndrome in patients with celiac disease (Gastroenterol 2013; 144: 912-17).

You-Tube LinkPatients With Celiac Disease Have a Lower Prevalence  – YouTube..Dr. Toufic A. Kabbani discusses his manuscript “Patients WithCeliac Disease Have a Lower Prevalence of Non-Insulin-Dependent Diabetes Mellitus and Metabolic Syndrome.”

A retrospective review of 840 patients with biopsy-confirmed celiac disease were compared with 840 random matched controls.  Controls were matched for age, sex, and ethnicity.  Mean age was 49.4 years.

Key findings:

  • 26 (3.1%) of celiac disease cohort and 81 (9.6%) (p <0.0001) had NIDDM.
  • 3.5% of celiac disease cohort and 12.7% of controls had metabolic syndrome.
  • Though celiac disease patients had lower BMI, these findings were still present after controlling for this variable.
  • Prevalence of NIDDM was strongly associated with age in both groups.  In celiac cohort, NIDDM occurred in 0% (n=343) of those <45, 3.1% in 45-64, and 9.3% in those >65.  In contrast, the control group had NIDDM in 3.5%, 11% and 19.3% respectively.

With regard to pathophysiology, the authors did not think the protection from NIDDM was related to malabsorption.  Evidence of malabsorption was more common in patients with CD and NIDDM than in those without NIDDM.

Related blog posts:

 

Drug Shortages and Selenium Deficiency

If you participate in the care of patients who are dependent on parenteral nutrition, then you are familiar with frequent component drug shortages.  Generally, attempts to manage these shortages involve rationing and targeting those with the greatest need.  In one institution, this was not effective in preventing biochemical deficiency of selenium (JPEN 2013; DOI 10.1177/0148607113486005).  Thanks to Kipp Ellsworth for this reference.

The authors describe five pediatric patients who were completely dependent on parenteral nutrition due to intestinal failure.  During a 9-month shortage of intravenous selenium, all five who were previously selenium replete had deficiency identified (level <20 ng/mL).

After these deficiencies were identified, the patients were placed on Multitrace-5 (MTE-5).  This multivitamin contains 20 mcg/mL of selenium.  While patients prior to the shortage typically received 50-75 mcg/day, after instituting MTE-5, they received 10-26 mcg/day.  Nevertheless, this helped prevent any clinical evidence of deficiency.  In patients with selenium deficiency, there is an increased risk of cardiomyopathy, chronic illness, and death.

The authors note that their preference is to individually dose the specific trace elements and that MTE-5 can contribute to elevated levels of manganese and chromium with long-term usage.

Related blog links:

Related references:

  • -Gastroenterol 2009; 137: S61-S69.
  • -J Pediatr 2011; 159: 39.

An easy tool to assess cardiometabolic risk

There are a large number of anthropometrics to assess nutrition; however, simplifying the assessment would facilitate broader usage.  To that end, a recent publication suggests that checking triglyceride level and waist circumference is helpful to identify cardiometabolic risk (J Pediatr 2013; 162: 746-52).

This study used a cross-sectional design; anthropometrics, biochemistries, and cardiorespiratory fitness were assessed in 234 participants between 10-19 years of age.

Specific measurements included the following: weight, height, waist-to-height ratio (WHTR), lipid panel, blood pressure, and a cardiorespiratory fitness (CRF) as assessed by a progressive cycle ergometer tests.  The authors defined a HW or hypertriglyceridemic waist phenotype characterized as having a triglyceride ≥110 mg/dL and a waist circumference ≥ 90% for age/sex.

Key findings:

  • Participants with the HW phenotype were unlikely to have a high CRF (OR 0.045).  In addition, they had a high likelihood of elevated LDL (OR 4.41), impaired fasting blood glucose (OR 3.37).
  • Those with high WHTR were at higher odds for having low HDL (OR 2.57), high diastolic BP (OR 3.21) compared with normal WHTR participants.

Lunchroom Makeover

A recent pilot study indicates that $50 and three hours can increase the chances that teens will eat their fruits and vegetables (J Pediatr 2013; 162: 867-9).  While the US Department of Agriculture has mandated alterations in what foods that schools offer for lunch, schools cannot force students to eat specific foods.  As such, the authors tried changing the convenience, attractiveness, and ‘normative nature of healthy foods’ in the lunchroom. These changes are part of a behavioral science called “libertarian paternalism.”

These field studies took place at two schools in western New York with students at 7-12 grade levels.  After implementing changes in the lunchrooms, researchers recorded tray waste on multiple dates.

Specific changes included the following:

Improved convenience:

  • “Healthy convenience line” with only submarine sandwiches and healthier sides (fruits/vegetables)
  • Salad served in see-through to-go containers

Improved attractiveness:

  • Lunch menu posted with nice color photos of fruits and vegetables
  • Fruit displayed in nice bowls or tiered stands

Normative behavior:

  • Verbal prompts by staff: “Would you like to try…”, “No veggie? How about…” “You can get another side with your meal. How about grabbing a piece of fruit?”
  • “Last chance for Fruit” sign displayed next to fruit basket at the cash register

The impact of the “smarter lunchroom:” actual fruit consumption increased by 18% and vegetable consumption increased by 23%.  The limitations of this study: no control school, did not track individual consumption, and small number of measured days.

Related blog link: