“Tummy Time” Not Needed

A recent NY Times article reviews a study which showed no benefit in motor development in babies who had “tummy time.”

Here’s the link: nyti.ms/11vrG11 

Here’s an excerpt:

Putting infants to sleep on their backs, recommended since the early 1990s, has helped reduce the prevalence of sudden infant death syndrome. ..Now a new study, published in May in the journal Early Human Development, suggests that tummy time may be irrelevant.

Canadian researchers compared 1,114 infants born from 1990 to 1992, just before the “back to sleep” campaign began, with 351 infants born 20 years later. They found no difference between the two groups in the age at which prone to supine or supine to prone rolling began, or in the order in which those behaviors appeared….

Whether tummy time helps or not, said the lead author, Johanna Darrah, a pediatric physical therapist at the University of Alberta, “the back to sleep campaign has not adversely affected motor development. Motor development happens.”

Codeine Contraindicated after Adenotonsillectomy

Due to concerns outlined previously (Why “therapeutic dose” of codeine can kill | gutsandgrowth), the FDA has now placed a boxed warning on all codeine-containing products and is now contraindicated after adenotonsillectomy.  This is reviewed in a recent perspective article: NEJM 2013; 368: 2155-57.

“In the case of codeine, a combination of case reporting and our evolving understanding of genetic influences on drug response has clarified the need to avoid this drug after adenotonsillectomy.”

Bottomline: Due to the variability in codeine metabolism, alternative narcotic agents are usually a better choice even in those who have not undergone adenotonsillectomy.

What to Feed Your Baby

“What to Feed Your Baby” — is the title of a recent, easy-to-read, practical book written by one of my colleagues, Stan Cohen.  I had the opportunity to read it and recommend it as an excellent resource for parents.  This book is not just for selecting formula and introducing foods, but it also reviews gastroesophageal reflux, colic, stooling problems, poor weight gain, overweight issues, prematurity, and allergies.  In addition, the subtitle, “Cost-Conscious Nutrition for Your Infant,” is an important element throughout the book.

The first few chapters highlight the advantages of breastfeeding but acknowledge that formula-feeding is an acceptable alternative.  Specific advantages that are outlined in Table 2.2 include decreased infections, decreased risk for several illnesses like sudden infant death syndrome (along with many others like diabetes and obesity), protection from allergies, and improved intelligence.  Advantages for the mother, like weight loss and better emotional health, are discussed as well.

Almost any question that a new mother would ask about the logistics of breastfeeding are answered in the 3rd chapter: “How long should each feeding be?” “Should I wake the baby?” “Do I need to stop if I have a cold?” “How long can the breastmilk be stored?”  The latter question has its own table 3.1 and the answer depends on the storage temperature.  At room temperature, covered breastmilk should be durable for 6-8 hours.  In addition, Dr. Cohen explains the need for vitamin D supplementation.

Chapters 4 and 5 help parents understand the highly marketed formulas and to understand a rationale for choosing one formula over another, including cost as a factor.  Dr. Cohen provides data on mean docosahexaenoic acid (DHA) content in breastmilk throughout the world.  In the U.S., the level is relatively low at 0.29 (as a percentage of fatty acids).  The breastmilk DHA level is nearly three times higher in Japan and Artic Canada.  These discrepancies account in part why formula companies may choose different target concentrations for some of their components when trying to mimic breastmilk.

While Dr. Cohen explains that some of the differences between formulas are akin to differences between Coke and Pepsi, he expresses a preference for the current Mead Johnson formula Enfamil Premium due to its higher DHA content –“though the research is not thoroughly established.”  However, he states that the differences probably do not justify a much higher cost.  For a generic brand, the Costco brand, “Kirkland Signature…are reasonable and less expensive, FDA-approved options.”

In addition, these chapters question whether infant organic formulas are truly organic (page 55), explain the issue of burping, and discuss the pragmatic advise regarding cleaning nipples/bottles; “kitchen clean” with soap and a washing with hot water should suffice and sterilization is not needed.

The most inciteful comments, in my opinion, are in chapter 5:

  • Lactose-free formulas: “Mead Johnson pulled its product from the market because lactose sensitivity is rare, rare, rare in infants…Abbott, in a shrewd marketing move, renamed its formula, originally called Lactofree, to Similac Sensitive, and that labeling has convinced an enormous number of mothers that this formula makes a difference.”  Similac Sensitive accounts for >10% of formula market.  A similar product is Gerber (previously Nestle) Good Start Soothe.
  • Elemental formulas: “cost as much as a monthly Porsche payment.”  Monthly costs of each type of formula are detailed in Table 5.3.  Routine cow’s milk based formula $149.88, soy-based $153.56, cow’s milk with rice starch $159.39, hydrolyzed (broken down protein) formula (e.g.. Alimentum, Nutramagen) $223.56, and elemental amino acid based $511.83.
  • Among extensively hydrolyzed formulas, Dr. Cohen indicates a preference for Alimentum (from Abbott) over its competitors due to better acceptance by infants.
  • The rationale for not switching from contracted WIC products is explained.  When changing from a contracted product to a non-contract product, the costs are much greater and among the same type of formula there is not a scientific rationale.
  • Reasons why goat’s milk are not a good choice and “dangerous” for infants are detailed.  “The protein content is over three times higher than cow’s milk…additionally, goat’s milk is deficient in folate and vitamin B6.”

As noted above, the book covers a variety of pediatric gastroenterology problems in the newborn.  As part of the chapter on undernutrition, additives to increase calories are detailed (pg 136).  For example, a tablespoon of polycose adds 23 cal, a tablespoon of rice cereal 15 cal, and  a tablespoon of vegetable oil 124 cal.

The last few chapters provide ample advice on transitioning to solid foods, reviews nutrients and mineral oils.  In addition, he provides growth charts (for full term, premature infants, and infants with Down syndrome) as well as tables on infant formula contents.

Take-home message: this is a terrific resource for parents to help understand the what, why and when of feeding their infant.  At the same time, the book provides advice on the most common pediatric gastroenterology problems of infancy like reflux, colic, stooling difficulties, allergies, and poor weight gain.

Book’s website and how to purchase:

http://www.what2feedyourbaby.com

To purchase the book:

Here is the link:

Reviews:

Other favorable reviews (http://what2feedyourbaby.com/reviews/) have come from influential pediatricians like Jay Berkelhammer and pediatric gastroenterologists like Jeff Hyams and Allan Walker.

In this book, Dr. Stanley Cohen, a pediatric gastroenterologist and nutritionist with longstanding interest in infant nutrition, provides a practical and pragmatic approach to a major concern for new mothers, namely What to Feed Your Baby.

— Allan Walker, M.D., director, Division of Nutrition, Conrad Taff professor of pediatrics and nutrition, Harvard Medical School

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Sugar-resistant bugs

“Evolution helps cockroaches lose their sweet tooth, increase survival”

An excerpt from the following link: Evolution helps cockroaches lose their sweet tooth, increase   summarizes a recent study from Science below.  The findings provide further evidence of how bugs (along with microbial bugs) adapt; in circumstances where glucose can be lethal, bugs that are sugar averse have a selective advantage.

Have you ever wished you could just turn off your sweet tooth to help you resist that third piece of pie? For people, the downside of the deliciousness of sugar is simply feeling really full or gaining weight, but for cockroaches, their sweet tooth can be deadly.

The poisoned baits people set to kill roaches in their homes lure the unsuspecting insects in with sugar. But it turns out that the selective pressure of delicious, deadly traps throughout the environment has led to the rapid evolution of cockroaches that avoid sugar. They turned the sweet tooth off—or rather redirected it so it now tastes bitter.

A team of researchers from North Carolina State University published research this week looking at how the German cockroach, Blattella germanica, was able to adapt so quickly when surrounded by tasty insecticide. Sweet baits became popular for roach control in the mid-1980s, but several years later scientists began noticing a new behavioral trait: aversion to glucose, the most common simple sugar. The trait is heritable, and cockroaches with it avoided the baits. In areas treated with these traps, the roaches without a sweet tooth had much better survival rates than the roaches that lacked this new adaptation.

Insects’ sense of taste comes from hair-like structures on the mouthparts that contain nerve cells called peripheral gustatory sensory neurons. Insects have four “tastes”—sweet, bitter, water, and salt. Typically, foods that trigger the sweet neurons led the insects to eat, while foods that trigger the bitter neurons cause them to avoid that food.

The scientists, Ayako Wada-Katsumata, Jules Silverman, and Coby Schal, suspected that a change in the bitter and sweet sensory systems led to the glucose aversion trait. When they compared the sugar and bitter sensitivities of the averse roaches with the wild type, they found that the glucose triggered the same neurons as caffeine — very bitter. However, both groups of roaches still ate fructose, another simple sugar molecule, at the same rates.

Sampling wild cockroaches, they found glucose-averse individuals in seven out of 19 populations. The sensory responses in the native cockroaches mimicked the lab experiments, with caffeine and fructose responses remaining normal and glucose triggering the bitter system instead of the sweet. This shows that a very similar glucose aversion mechanism arose in multiple populations.

What kind of mutation led to this adaptive behavior? The researchers suspect that one or more mutations modified the bitter sensing system to react to glucose. For populations surrounded by sweet poisons, this mutation offers a serious evolutionary advantage. However, growth and reproduction of the glucose-averse roaches is slower than the normal population, so the mutation only functions as an adaptation in the face of attempted pest control.

The more we try to poison the roaches, the greater the advantages of being a cockroach that thinks sugar tastes bitter, and the more common this mutation will become. We probably need to find a new type of insecticide.

Science, May 2013. DOI: 10.1126/science.1234854

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Breaking down lung defenses in Cystic Fibrosis

Cystic fibrosis patients develop chronic neutrophilic inflammation of the airways.  Neutrophils which help fight off bacterial infections also release peroxidases and proteases which can damage the lung tissues.  Neutrophil elastase which is one of the proteases elaborated by neutrophils can digest elastin; this is prevented by α-1-antitrypsin.  However, when there is excessive free neutrophil elastase this can overwhelm this protection.  A recent study has shown that neutrophil elastase activity in bronchoalveolar lavage (BAL) at 3 months of age was associated with early bronchiectasis (NEJM 2013; 368: 1963-70).

Design: 127 consecutive infants (from region of Western Australia) who were diagnosed with cystic fibrosis after newborn screening were recruited; however, 10 were too young and 3 were lost to followup due to relocation.  Most were followed for 3 years; 78 remained in the study at 36 months. Chest CT scans and BAL were performed at 3 months, 1 year, 2 years, and 3 years when patients were in stable clinical condition.

Bronchiectasis was identified by CT scan findings: “defined as a bronchus-to-artery ratio of more than 1.0 or the presence of a non tapering bronchus in the transverse plane.”

Key findings:

  • Point prevalence of bronchiectasis: 29.3% at 3 months, 31.5% at 1 year, 44.0% at 2 years and 61.5% at 3 years.
  • Free (unbound) neutrophil elastase activity in BAL fluid was a risk factor for bronchiectasis with an odds ratio of 3.02.  At 3 months of age, 23.3% had detectable neutrophil elastase activity in BAL fluid.
  • Other risk factors for bronchiectasis included meconium ileum (OR 3.17), and respiratory symptoms at time of CT (OR 2.27).

Take-home message: Damage happens to the lungs early in life. The related editorial (pg 2026) states “early cystic fibrosis lung disease is not ‘silent’ if you listen carefully.” To improve long-term outcome, early intervention will be necessary.

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Overlooking Important Detail$ in Hereditary Angioedema Treatment

Several approved treatments are now available for Hereditary Angioedema (HAE) attacks. A recent article highlights the effectiveness in 46 children who received 2237 infusions of nanofiltered C1-esterase inhibitor (C1 INH-nf) treatment (J Pediatr 2013; 162: 1017-22).

Background:  HAE prevalence: 1 in 50,000.  Though it is inherited in an autosomal dominant manner, up to 25% of case are de novo. HAE is characterized by recurrent episodic attacks of subcutaneous edema of the skin, GI tract or upper airway.  Symptoms often present between 4 and 11 years of age.  GI tract symptoms are often recurrent colicky abdominal pain. Triggers for attacks may include infections, emotional stress, and trauma (e.g. bodily contact from play).

This manuscript provides data from 4 prospective clinical trials of  C1 INH-nf (Cinryze).  Most children in this study responded within 30 minutes compared with 2 hours for placebo.  Therapy also reduced the rate of attacks.  One interesting aspect of the study was its lack of any mention of cost.

From UptoDate:  “Cost of first-line therapies — All first-line therapies for acute attacks of HAE are costly. In the US, the cost of one treatment with C1INHRP,ecallantide, or icatibant ranged from $5000 to $10,000.”  Hereditary angioedemaTreatment of acute attacks – UpToDate

From a Hereditary Angioedema – RegenceRx website: “As a preventative therapy, C1 esterase inhibitor (Cinryze) is significantly more costly than other formulary alternatives (~$500,000 per year; ~250 times more than danazol). For acute treatment of an HAE attack, C1 esterase inhibitor (Berinert) and ecallantide (Kalbitor) costs approximately $6,000 to $10,000 per attack. Cost may double if re- treatment is needed within 24 hours.”

Additional reference:

  • -Eur J Pediatr 2012; 171: 1339-48.  Consensus of therapeutic strategies for HAE.

Spina Bifida, Humility, and Quality of Life

While a recent article (J Pediatr 2013; 162: 993-98) on spina bifida and its effect on quality of life provide useful information, the accompanying editorial by John Freeman (J Pediatr 2013; 162: 894-95) had much broader implications for me.

The referenced article provides data showing the effects of spina bifida on quality of life QOL), even in those who reported their current health as good.  The tools that the investigators used for 40 youth and 13 young adults were the HUI-3 and AQoL.  Both of these tools correlated health-related QOL (HR-QOL) and the level of the anatomic lesion; those with thoracic/higher lesions had worse HR-QOL.

Some of the points made by Dr. Freeman:

  • Quote at start: “Health: A state of complete physical, mental, and social well-being and not just the absence of sickness or frailty.” –World Health Organization
  • In 2004, he followed up with two patients who he had presumed to be quite successful.  Both “were living at home, wheelchair-bound, with high paraplegias.  Both were community college graduates and employed….When I asked them what I should tell parents delivering a newborn with spina bifida, each replied, ‘I wish I had never been born.’ I was shocked.”
  • He notes that the referenced article had a low participation rate (39%) which could introduce significant biases.  “Were the respondents those with greater or less disability?”
  • Conclusion: “I will not presume to have answers to these questions but propose further discussion of the quality-of-life issues…on decisions regarding early treatment of spina bifida.”

These studies make it clear that some children with spina bifida, particularly those with higher lesions, have poor HR-QOL.  The broader implication is that many children/adults who we think are doing pretty well do not see it that way.  Trying to determine what the future holds for children with chronic health problems in infancy is difficult.  Even in the most severe diseases, most parents want everything done.  Will this type of information change anything?

The Paradox of Vaccine Resistance

A recent editorial highlights the fact that the “last mile is the longest” when it comes to eradicating diseases with vaccines (NEJM 2013; 368: 1374-75).  The point the authors make is that as vaccines become successful, there is increasing refusal in communities to receive vaccines.  Few individuals may have direct or indirect experience with vaccine-preventable diseases when initial efforts are successful.

Much like bacterial resistance to antibiotics, individuals may become resistant to the use of vaccines when the perception of their utility dissipates.  As such, the authors note that eradication efforts going forward must not be a half-hearted effort. “If a disease such as measles is considered a priority by the global public health community, human and financial resources should be committed up front to a full-scale eradication initiative.”

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Childhood Obesity and Consensus Recommendations

Everyday pediatric gastroenterologists care for obese children; in fact, the prevalence is approximately 17% in the United States (JAMA 2010; 303: 242-9).  The types of problems include the entire spectrum of pediatric gastroenterology, though some problems like encopresis and gastroesophageal reflux are more prevalent in this population.  Whether during visits for other problems or at clinic visits focused on obesity, there may be opportunities to improve the health of these patients.

A recent consensus statement provides some guidance on the problems and treatment approaches (JPGN 2013; 56: 99-109).

After reviewing epidemiology and etiology, the consensus reviews common comorbidities which include

  • NAFLD/NASH
  • Cardiovascular: Hypertension, Hyperlipidemia   Screen: Blood pressure, fasting lipids
  • Pulmonary: Obstructive sleep apnea  Screen: assess snoring
  • Psychiatric: Depression, Bullying   Screen: assess clinically
  • Orthopedic: Blount disease (pain at medial aspect of knee) and difference in leg length, SCFE
  • Endocrine: Diabetes/insulin resistance, Polycystic ovarian syndrome  Screen: look for acanthosis nigricans, fasting glucose, hemoglobin A1c.  For PCOS, inquire about oligo/amenorrhea, look for hyperandrogenism, consider pelvic ultrasound

Besides looking for these comorbid conditions, the authors discuss treatment.  “Overall, multidisciplinary, behavior-based programs should be used when lifestyle modification counseling has not worked.”  Also, the authors recommend motivational interviewing, lifestyle interventions (healthy activity and diet =”mainstay of weight management”), possibly using Orlistat, and possibly bariatric surgery.

These consensus recommendations are sensible.  Will they make a difference?

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Vaccine successes and ambitions

“Designing Tomorrow’s Vaccines” is a fascinating assessment of the success of vaccines as well as a look into the what future vaccines may accomplish (NEJM 2013; 368: 551-60).

First, I like the quote from Thomas Jefferson noted in the article:

“I avail myself of this occasion of rendering you a portion of the tribute of gratitude due to you from the whole human family.  Medicine has never before produced any single improvement of such utility…mankind can never forget that you have lived. Future nations will know by history only that the loathsome small-pox has existed and by you has been extirpated.”  Letter to Edward Jenner (May 14, 1805).

Jefferson’s enthusiasm was not without merit.  “In the 20th century alone, smallpox claimed an estimated 375 million lives.”  Yet, “since 1978, not a single person has died from smallpox.” Unfortunately, at this time, every year “more than 1.5 million children (3 per minute) die from vaccine-preventable diseases.”

Previous success in the U.S: Comparison of the estimated number of cases per year in the 20th century with the number of deaths in the year 2002 from the same diseases:

  • Poliomyelitis: 1.63 million vs 0
  • Diptheria: 17.6 million vs 0
  • Measles: 5.03 million vs 36
  • Pertusis: 1.47 million vs 6632
  • Rubella: 4.77 million vs 20
  • Smallpox: 4.81 million vs 0

Despite these advances, vaccines have “yet to realize their full potential.”  Effective vaccines are needed for malaria, HIV, and tuberculosis.  Vaccines for influenza which rely on 50-year-old technology need to be improved.

So how can this be achieved?

  • Improved knowledge of atomic structure/structural biology has provided new insights into neutralizing antibodies along with specific antibody reactions. This can counter immune evasion by targeting highly conserved regions
  • Millions of gene sequences encoding antibodies within a single individual can be analyzed to improve vaccine design
  • Genomewide sequencing of microbes has improved selection of vaccine targets
  • Improvements in delivery systems, like using viruslike particles or nanoparticles; alternatively, gene-based delivery of vaccines is feasible
  • Recombinant techniques has allowed a shift from egg-based methods

What is not on the horizon  — a vaccine for the half-truths that permeate the discussion.

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