Maternal Obesity and Neurodevelopmental Outcomes

If there were not enough reasons to be concerned about the prevalence of obesity already, here’s another: there is growing evidence that maternal obesity (i.e. obesity in the mother at the beginning or prior to pregnancy) is associated with an increased risk for a number of neurodevelopment outcomes (J Pediatr 2014; 165: 891-6).  According to this medical progress report, there are a number of limitations in interpreting the studies associating obesity with these outcomes.

  1. Unclear what is the best measure of obesity and the best timing of measuring obesity
  2. “It is unclear whether obesity per se is the entity that causes adverse outcomes, or whether  obesity is only a marker for other factors” (eg. diet and activity)

With these limitations in mind, the authors review a number of studies.  Key points:

  • Cerebral palsy: “a dose-response relationship was seen, with any diagnosis of maternal obesity carrying a relative risk (RR) of 1.30 (95% CI 1.09-1.55) for CP.  With any diagnosis of morbid obesity, the RR was 2.70 (CI 1.89-3.86)
  • Autism: the risk of developing ASD (OR 1.67; CI 1.10-2.56) and NDD [neurodevelopmental delay] (OR 2.08; CI 1.20-3.61)
  • Cognitive deficits: maternal BMI “was inversely associated wit age 5 years IQ”
  • Behavioral/psychiatric disorders: “children of women who were both overweight and gained excess weight during pregnancy had a 2-fold (OR 2.10; CI 1.19-3.72) increased risk of ADHD symptoms compared with offspring of normal-weight women.” Also, some studies have shown an increased risk for schizophrenia in children of mothers with BMI >30.

Bottomline: obesity is not good for individuals and is associated with increased neuodevelopmental risk in offspring as well.

 

NASPGHAN Postgraduate Course 2014 -3rd Module

This blog entry has abbreviated/summarized the presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.  All of the speakers had terrific presentations.  The course syllabus is attached:

PG Course Syllabus 2014

The 3rd Module had a “potpourri” of GI problems.

Extraesophageal Manifestations of Gastroesophageal Reflux –Ben Gold, MD (GI Care For Kids, Atlanta) (pg 86)

Is reflux really the scurge of the earth and the cause of every malady known to human-kind in the head, neck, and lungs…?

Key points:

Airway protection: “Aerodigestive disease reflexes are intact by 38 weeks gestation.”

Central deglutition apnea: a normal protective mechanism to prevent aspiration during swallowing. (Hasenstab KA, Jadcherla, S. J Pediatr 2014; 165:250-255).  No proof at present that central apnea is caused by reflux though there is a biologic plausibility.

“Although reflux causes physiologic apnea, it causes pathologic apneic episodes in only a very small number of newborns and infants.”  “When reflux causes pathological apnea, the infant is more likely to be awake and the apnea is more likely to be obstructive in nature.”

Laryngeal Reflux:

  • Chronic cough, chronic laryngitis, hoarseness, and asthma may be associated with GERD BUT the data showing a relation between reflux and upper airway disease are weak
  • Airway symptoms attributed to reflux in adults include hoarseness, chronic cough, and globus sensation
  • Affected adults rarely have typical reflux symptoms
  • The sensitivity of laryngoscopic findings to identify reflux disease are poor. Sherman et al. Am J Gastroenterol. 2009;104:1278-95. Vandenplas et al. J Pediatr Gastroenter Nutr. 2009;49:498-547.

Asthma:

“Chronic cough, chronic laryngitis, hoarseness and asthma are multifactorial disease processes and acid reflux can be an aggravating cofactor.” GER is an unlikely contributor to asthma if reflux testing is negative.

“Two NIH-funded blinded, randomized placebo-controlled trials (RCT), one in adults (using esomeprazole), one in children (using lansoprazole) showed NO difference in asthma outcomes comparing placebo and acid suppression therapy”

Multi-Channel Intraluminal Impedance/pH probe studies: Pediatric studies are critically needed to determine if knowing the amount of nonacid reflux changes treatment or outcome

Proton Pump Inhibitors can cause gastric bacterial overgrowth (Rosen R et al JAMA Pediatr 2014; JAMA Pediatr. doi:10.1001/jamapediatrics.2014.696)

Ben Gold (speaker) and Jay Hochman prior to 5K Run

Ben Gold (speaker) and Jay Hochman prior to 5K Run

Related blog posts:

EoE: PPI, PPI-REE, TCS, OVB, SFED, 4FED….…Alphabet Distress — Sandeep K Gupta, MD (Indiana University) pg 105 in Syllabus

Treatment endpoints discussed -histologic, symptomatic, fibrosis, etc.

  • Proton pump inhibitor responsive eosinophilic esophagitis (PPI-REE) may work by blocking STAT6 binding to Eotaxin-3 promoter rather than by acid suppression (PLos ONE 2012;7:e50037).  PPIs work (eos <6/hpf) in in 30-40%.  May need high dose to work long-term (Dr Molina-Infante – DDW 2014)
  • Topical corticosteroids (TCS) -higher dose = better response.  (Budesonide. Gupta SK, Vitanza J, Collins, MH Clin Gastro Hepatol 2014 [ePub], Fluticasone. Butz BK. Gastroenterology 2014). Clinical symptoms do not correlate with histologic response. Discussed long term safety concerns.
  • Reviewed diets -elemental, targeted, 4-food elimination and 6-food elimination.

Related blog posts:

“Gotta keep on movin”: New tricks and treatments for motility disorders –Carlo DiLorenzo (Nationwide Children’s Hospital) pg 116 in Syllabus

Key points:

  1. Most important motility study is a normal study.  If normal study, then there is more concern for sensory dysfunction.   Look for significant findings on motility studies not minor changes.
  2. Key to confirm if motility disorder is present. Hx/o small intestinal transplant in medical child abuse/Munchausen syndrome by proxy (Trans Proc 1996; 28: 2790)
  3. New tool: wireless motility capsule (J Pediatr. 2013;162:1181-7)
  4. Easier to obtain full thickness biopsies (Gastrointest Endosc 2011;73:949-54)

Treatments reviewed -“try everything”

  • prucalopride (JPGN 2014; 57: 197-203
  • cisapride -still available
  • lubiprostone (JPGN 2014;58:283–291)
  • linaclotide boxed warning not for <17 years of age –though has been used by motility specialists
  • cyproheptadine (J Pediatr 2013; 163: 261-7) –use in dyspepsia
  • fludrocortisone -used in orthostatic intolerance
  • augmentin -for small bowel motility (JPGN 2012;54: 780–784)
  • octreotide -for bowel motility
  • pyridostigmine (Colorectal Disease 2010 12, 540–548)
  • iberogast
  • botulinum toxin (Gastrointest Endosc. 2012 ;75:302-9)
  • treat bacterial overgrowth
  • surgery: Jube, GJ tube, ileostomy. “Every child with pseudoobstruction on TPN needs a gastrostomy and an ileostomy –(me, now)”
  • gastric electrical stimulation
  • emerging treatment: Elobixibat (for constipation) Expert Opin. Investig. Drugs

Related blog posts:

What’s New in the Diagnosis and Management of Constipation –Manu Sood (Children’s Hospital of Wisconsin) -page 130 in Syllabus

Reviewed recent guidelines from NASPGHAN

“Miralax is considered a 1st line agent”

Outcomes in children with constipation:

  • Almost 50% of patients experienced at least one relapse in first 5 yrs.
  • Almost 20% of children were symptomatic at 10 yrs. follow up (Bongers ME, et al. Pediatrics. 2010)

Pointers:

  • Slow transit is common
  • Rectal compliance does not predict success with treatment. Van den Berg MM, et al. Gastroenterology 2009.  Patients with mega-rectum may have motility disturbance as well.
  • Success rates for antegrade continence enemas (ACE) 65% to 89%. Colon manometry can help predict ACE success.  Up to 40% may be able to stop ACE w/in 2 years

Related blog posts:

N4K –Nutrition4Kids

I wanted to let followers of this blog know of a website which was developed under the guidance of one of my partners, Stan Cohen.  The website Nutrition4kids.com has a wealth of information and resources on nutrition topics.  In addition to Dr. Cohen, the group of medical advisors includes Mel Heyman, Bailey Koch, Kylia Crane, David Cohen, W Allan Walker, and Kathleen Zelman.  The official rollout for the website was this past week.

About N4K (from website): N4K is a personal, trustworthy, and expert guide to learning about and making the right food choices for your individual child regardless of age, cultural norms, medical conditions or food sources. Parents trying to feed their kids well are faced with inconsistent and misleading labelling of food products. “All Natural,” “Reduced Fat,” “Reduced Sugar,” “Made with Real Fruit,” “Green” and other terms are all but useless when making good food choices.

NASPGHAN Awards 2014

I wanted to congratulate/recognize this year’s awardees at NASPGHAN and to summarize some of the associated presentations.

This blog entry has abbreviated/summarized the presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

Major Awards:

  1. Harry Shwachman Award: Peter Whitington (Children’s Hospital of Chicago) This award is given for major life long scientific contribution to the field of pediatric gastroenterology.
  2. Distinguished Service Award: Melvin Heyman (UCSF Division Chief and JPGN editor). This award is given for excellence and service in the field of pediatric gastroenterology.
  3. AAP Murray Davidson Award: Jeffrey Hyams (Division Chief Connecticut Children’s)This award is given to an outstanding clinician, scientist and educator.

Fellow Research Award: “Bile Acid Signatures in Children Confer Protection From Clostridium Difficil Infection” ME Tessier et al (Baylor College of Medicine). Conclusions: Stool bile acids profiles are different in children with C difficile infection and could be a predisposing factor.  C diff toxins may alter bile acid profiles via inducing epithelial FGF-19 production.

Young Investigator Award “Analysis of Candidate Genes by Whole Exome Sequencing in Very Early-Onset IBD” J Kelsen (CHOP), et al. VEO-IBD cohort. Excellent presentation! (Related blog post: Just the Beginning: Mutations in Very Early Onset ..)

  • Children <5 years/extensive controls.
  • Mutation Findings: IL10RA/IL21R variants, RAG2/PIK3R1 variants
  • Presentation included phenotypic description (clinical and immunity/functional analysis)
  • Gut microbiome development being studied as well
  • Trying to combine microbiome data with genomic data.

William Balistreri Prize “A Prospective Newborn Screening Study for Biliary Atresia” Sanjiv Harpavat (Baylor College of Medicine) et al.   Excellent talk!

Background: 67 infants with biliary atresia (2007-2014) on retrospective review—ALL had elevated conjugated/direct bilirubin levels in first 24-48 hours of life. (Related blog post: Diagnosing biliary atresia earlier | gutsandgrowth)

Repeat testing at 2 weeks can identify those infants that need to be followed closely.  Workup needed for those who remained abnormal at 2 weeks of life.

This algorithm was studied at 4 different hospitals in Houston with 2-12% premature infants)

In newborn period:

  • N=11,636 –121 abnormal on newborn testing (based on hospital’s normative values -usually direct bilirubin >0.4)
  • When repeated at 2 weeks: 102 of these 121 were normal/only 12 continued to test high (2 with BA, 1 A1AT, 1 Rh disease, 8 resolved).  The two patients detected with biliary atresia is in line with the expected frequency of ~1 in 5000.
  • 7 missed retesting. 3 died (congenital heart disease), 2 missed followup, 2 had PCP refuse retesting.
  • Testing results: 100% sensitivity. Good specificity with repeat testing.

Baylor Workup approach to cholestasis:

  • 3-4 day evaluation
  • Day 1: liver panel, A1AT typing, U/S, CXR
  • Days 2-4: liver biopsy/percutaneous cholangiogram, +/- Kasai

Current AAP recommendation (per Ronald Sokol) is for all infants to have fractionated bilirubin.

Take-home message: How can we diagnose every infant on time? Possibly check every infant for direct/conjugated bilirubin in first 48 hours.

Young Clinical Investigator Award: “Poop-MD: A mobile health application accurately identifies acholic stools.” Douglas Mogul

Problem of delayed diagnosis has been improved in some studies with stool color cards. With emergence of smart phones (80% of 18-35 year olds have smart phones), opportunity to identify echoic stools with new technology.

  • PoopMD. Software determines whether stool is bloody, acholic, etc. Can email doctor and place reminder. FREE app.
  • Parents takes the picture of stool and then app analyzes.
  • Pilot study with 45 initial photographs reviewed by panel of 7 pediatricians
  • When at least 6 physicians agreed on stool color as being acholic (n=7), this was tested against app
  • App: 100% sensitivity for acholic stools. 89% specificity.
  • Working on Spanish version and improved interface.

Other awards:

NASPGHAN Foundation Awards

NASPGHAN Foundation Awards

Sponsored Awards

Sponsored Awards

NASPGHAN Postgraduate Course 2014 -Nutriton Module

Thanks to those who attended yesterday’s talk (10/24/14) at the clinical practice session and to those who provided helpful feedback.

This blog entry has abbreviated/summarized the presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.  If you make it to the bottom of this post, you will find some useful patient resources along with previous related blog entries.

Diet and the Microbiome –Robert Baldassano (CHOP) pg 140 in Syllabus

This was a very effective lecture; it brought together a lot of useful information.

Trying to sort out balance between health and disease and role of dysbiosis (altered microbiome)

  • Things that we ingest such as food (diet), antibiotics, and xenobiotics shape the composition of the gut microbiota and serve as substrates for the gut microbiota to produce metabolites
  • We are not the only organism consuming what we eat

Specific studies:

  • Wu G, et al. Science. 2011 Oct 7;334(6052):105-8  The Bacteroides enterotype was highly associated with animal protein and saturated fats, which equates to frequent meat consumption as in a Western diet. The Prevotella enterotype high values for carbohydrates and simple sugars, indicating association with a carbohydrate-based diet more typical of agrarian societies.
  • De Filippo C, et al. PNAS 2010: 14691-96: African children (compared with European) with more bacterial diversity & richness along with higher levels of short-chain fatty acids
  • Holmes et al. Cell Met 2012; 16: 559. Diet serves as a substrate for the microbiota to produce certain metabolites.

IBD and diet (Hou JK et al. American Journal of Gastro 2011;106:563-73)

  • High dietary intakes of total fats, PUFAs, omega-6 and meat were associated with an increased risk of CD and UC
  • High fiber and fruit intakes were associated with decreased CD risk
  • High vegetable intake was associated with decreased UC risk.
  • Consumption of meat, particularly red and processed meat increased the likelihood of relapse (Jowett et al Gut 2004)
  • Enteral diet for IBD can improve stool calprotectin within 1-2 weeks.

Take-home messages: Don’t tell your patients with non-stricturing IBD to eat a low fiber diet.  Reduced red meat and reduced oral iron may be helpful.  Vegetarian diet and Mediterranean diets may be helpful.

Related blog posts:

FODMAP: Navigating this Novel Diet –Bruno Chumpitazi, MD, MPH (Texas Children’s Hospital) -page 152 in Syllabus

  • Fermentable Oligosaccharides Disaccharides and Polyols (FODMAPs): Poorly absorbed, osmotically active, rapidly fermented (produce gas)
  • Higher FODMAPs increase breath hydrogen (Murray K et al. Am J Gastroenterol 2014;109:110-9)
  • Higher FODMAPs increase stool/ileostomy output (Barret JS et al. Aliment Pharmacol Ther 2010;31:874-882,Halmos EP J Gastroenterol Hepatol 2013;28(Suppl4):25-28)

Evidence for use of low FODMAPs diet is best in adult irritable bowel syndrome.

  • Shepherd SJ et al. Clin Gastroenterol Hepatol 2008;6:765-71
  • Staudacher HM et al J Nutr 2012;142:1510-18
  • Ong DK et al. J Gastroenterol Hepatol 2010;25:1366-1373
  • Halmos EP et al. Gastroenterology 2014;146:67-75

Limited studies in children.

  • Chumpitazi BP et al. NASPGHAN 2014 abstract n=33 pediatric IBS.  Favorable response noted to low FODMAP diet.

Dietary recommendations were reviewed along with the caveat that obtaining the assistance of a dietician/nutritionist is recommended.

Resources:

Related blog posts:

Nutrition in the Child with Neurological Disabilities –Kathleen Motil (Baylor College of Medicine) pg 162 in Syllabus

  • Nutritional disorders are highly prevalent in children with neurological disabilities: 29-46% are underweight; 8-14% are overweight.
  • Improved nutrition improves behavior, activity level, improves growth, and reduces infections.
  • Cause of nutritional disorders mostly related to inappropriate dietary intake but other factors can play a role
  • Growth/anthropometric measures are key determinant of nutritional assessment
  • Key questions: Is child taking all day to eat? Is child choking with feedings?
  • Critical BMI <12 kg/m-squared
  • Goal for BMI ~25%

Reasons for gastrostomy:

  • Flat growth >6 months/weight below curve
  • Parental request
  • Medication administration
  • Aspiration

Resource:

www.feedingtubeawareness.com  This site contains a terrific PDF download which explains enteral tubes in an easy to understand style along with good graphics. “What You Need to Know Now, A Parent’s Introduction to Tube Feeding is the guide book that every parent wished they had when they were first introduced to feeding tubes.”

Related blog posts:

 

 

 

 

Lack of Value of Breakfast for Weight Loss

In contrast to previous reports (see previous blog: Skipping breakfast -boomerang effect for obesity …), a recent Study Indicates Lack of Weight Loss by Adding Breakfast (from USA Today).  Here’s an excerpt

Grandmothers, marketers and researchers alike have long touted breakfast as a must-have meal, praising its ability to rev up metabolism, stave off hunger, help calorie watchers keep their weight in check and improve concentration and cognitive function.

But for all the glowing endorsements, there have also been warnings against over-hyping the power of breakfast.

That concern was raised again this summer when a study comparing groups of overweight and obese adults dieters found that eating or skipping breakfast made no difference in how much weight was lost over a 16-week period.

“Our simple question was (when it comes to weight loss), does it help to eat breakfast? And the answer seems to be probably not,” says David Allison, director of the University of Alabama at Birmingham Nutrition Obesity Research Center and senior investigator of the study reported in the American Journal of Clinical Nutrition.

Early Antibiotics and Obesity

A recent JAMA Pediatrics study showed that early and frequent antibiotics were associated with an increase risk of obesity.  Here’s a link to the LA Times summary of this article:  Antibiotics and Obestiy (LA Times)

Here’s an excerpt:

Broad-spectrum antibiotics — including amoxicillin, tetracycline, streptomycin, moxifloxacin and ciprofloxacin — are intended for treatment of major systemic infections, in cases where the bacteria causing the illness has not been identified, or where a patient is under attack by a strain of bacteria resistant to standard antibiotics. While they can be highly effective, their antibiotic action is indiscriminate, and beneficial bacteria in the body are often killed off as collateral damage.

The latest study tapped the medical records of 64,580 babies and children in and around Philadelphia. It was published Monday [Sept 29, 2014] in the journal JAMA Pediatrics.

The heightened risk of obesity linked to antibiotic use was not huge: Babies who got wide-spectrum antibiotics in their first two years were about 11% more likely to be obese between 2 and 5 than were those who got no such drugs. Babies who had four or more courses of any antibiotics in the first two years were also 11% more likely to be obese in early childhood than those who’d had fewer exposures to antibiotics.

Related blog post:

On the Merits of Moderation: Salt, Cholesterol, and Vitamins

At excellent overview from NY Times that explains that strict reductions in salt and cholesterol may be detrimental and that additional vitamins may be harmful. Here’s the link: Dash of Salt Does No Harm

Here’s an excerpt:

The second New England Journal of Medicine study did just that. In addition to looking at high sodium diets, it also compared the health outcomes of those who had very low sodium diets. What they found was worrisome. When compared with those who consumed 3-6 grams per day, people who consumed less than 3 grams of sodium per day had an even higher risk of death or cardiovascular incidents than those who consumed more than 7 grams per day.

This result would be shocking if we in the medical community hadn’t seen it before. But we have. In 2011, researchers published a study in the Journal of the American Medical Asssociation after following 3,681 people over almost a decade. They, too, found that excessive salt intake was associated with high blood pressure. They also found that a low-sodium diet was associated with higher mortality from cardiovascular causes….

Why experts and organizations feel the need to go from one extreme to the other is unclear. But it’s unfortunately something we do far too often in medicine.

Take cholesterol. Initially, people believed that the evidence was pretty compelling that high cholesterol was bad for you…Eggs were shunned. But later research showed us that egg consumption had no relationship to cardiovascular disease for most people. In fact, a majority of people’s serum cholesterol level has little to do with how much cholesterol is in their diet. Today we use medications to lower our cholesterol levels. Once again, though, our sights keep shifting lower…

We have to learn that when one extreme is detrimental, it doesn’t mean the opposite is our safest course.

Preventing Picky Eating Habits

According to several studies in Pediatrics and summarized in NY Times, preventing picky eating habits and developing good diet habits relies on #1) introduction of fruits and vegetables in the first year of life and #2) avoid sugar-sweetened beverages in infancy.

NY Times Food Introduction Article

Here is an excerpt of the summary:

The package of 11 studies was published in the journal Pediatrics and was funded by the Centers for Disease Control and Prevention and the Food and Drug Administration, among others. Investigators tracked the diets of roughly 1,500 6-year-olds, comparing their eating patterns to those observed in a study that followed them until age 1…

As it turns out, “when infants had infrequent consumption of fruits and vegetables, they also had infrequent consumption at 6,” said Kelley Scanlon, an epidemiologist at the C.D.C. and the senior author of a few of the new studies.

Dr. Scanlon and her colleagues suggested that it is best to interest children in fruits and vegetables by late infancy — roughly between 10 and 12 months old.

Another study in the new series found that babies who consumed any amount of sugar-sweetened beverages were two times more likely to drink them at least once daily at age 6. A third study found that infants ages 10 to 12 months who were given sugar-sweetened beverages more than three times a week were twice as likely to be obese at age 6 than those who consumed none as infants.

Their analysis took into account factors that could skew results, like race, family income and breast-feeding. ..Breast-fed infants are more accepting of new foods than babies who drank the same-tasting formula day after day, research has shown. A C.D.C. study in the new series found that children who were breast-fed were more likely to consume water (versus sugar-sweetened beverages), fruits and vegetables at age 6.

Related blog post:

Sweetened Beverages -A Big Problem for Little Kids …

Reading Past the Headline: Low Fat vs Low Carb

A recent study purportedly showed that a low-carb diet is superior to a low-fat diet.  However, David Katz explains how this study was flawed.  Here’s the link: Huffington Post “Low-fat” versus Low-carb and here’s an excerpt:

It was published in the Annals of Internal Medicine.. Allegedly, the researchers compared a low-fat to a low-carb diet. But in fact, they compared a diet that allowed up to 30 percent of calories from fat to a diet that allowed up to 40 grams of daily carbohydrate…

baseline carbohydrate intake was 240 grams per day, so while fat intake was “trimmed” 5 percent, carbohydrate intake in that assignment was slashed 75 percent. This might have been billed “a study to compare a really big change from baseline diet to a really small change from baseline diet.”…

the low-carb diet, since it was actually low-carb, obviously was much more restrictive than the low-fat diet, which wasn’t actually low-fat. That had the predictable result: those on the low-carb assignment took in many fewer calories…

I am not an advocate of low-fat diets. I think the concept is obsolete. I am an advocate, based on the evidence, of wholesome foods in sensible combinations. That dietary pattern can be low or high in fat, relatively lower or higher in carbohydrate.

Related blog posts: