Better growth charts for preterm children

A community-based cohort study from the Netherlands involving 1690 preterm infants (25-36 weeks) and a random sample of 634 full term infants provides a more precise tool for monitoring growth over the first four years of life (J Pediatr 2012; 161: 460-5).

Key findings:

  • The lower the gestational age, the lower the median value for both weight and height.  A quick glance at their tables indicate that infants born at 25 weeks gestation remained on average about 2 kg and 4 cm smaller than full term infants.  Infants born at 32 weeks gestation were on average about 1 kg and 2 cm smaller through the study period.
  • The absolute differences in weight and height were nearly constant, indicating that there was a lack of ‘catch-up’ growth.  At the same time, a child ‘following his own curve’ parallel to growth curve is likely a normal pattern
  • Head circumference at the end of the first year was similar between preterm and term infants
  • Greater variability was noted in boys

While this study did not adjust for maternal height, it is known that short maternal height does correlate with increased likelihood of short offspring.  This is partly mediated by having a small for gestational age birth.  Other limitations of the study included that the cohort was >90% Caucasian, and there was no adjustment for multiple births.

Useful links/references:

  • Growth Charts – Homepage -CDC growth charts
  • Pediatrics 2011; 128: e1187-94.  Growth and predictors of growth restraint in moderately preterm-born children.
  • Pediatrics 2003; 112: e30-8.  Growth of preterm infants during 1st 20 years.

Closer followup for Celiac disease & pediatric guidelines

Data from the Mayo clinic indicate that Celiac patients are not followed up adequately (Clin Gastroenterol Hepatol 2012; 10: 893-99).

Data was extracted on 122 patients from Olmsted County.  Due to the Rochester Epidemiology Project, a comprehensive medical record is available for the entire county population (since 1966).

Results:

  • At 1 year following diagnosis, 41% of patients had followup visits; 89% within 5 years.
  • At followup visits, gluten-fee diet compliance was assessed in 33.6% and 79.8% respectively at 1 and 5 years.
  • The minority met with a dietician: 3.3% and 15.8% respectively at 1 and 5 years.
  • Serological followup was performed in 22.1% and 65.6% respectively at 1 and 5 years.

The related editorial (pages 900-901) makes the point that quality follow-up and outcomes would be aided by clear guidelines.  General guidelines in our practice are noted below.

When I review lists of patients with specific diagnoses, I am often surprised by the lack of follow-up for a number of conditions, not just celiac disease.  Developing a system to remind patients about follow-up for a wide range of conditions would be a worthwhile goal for pediatric practices.

Additional references/blog entries:

General Guidelines in our practice (developed by Dr. Jeff Lewis in 2009)
1. Who to test
There is a wide spectrum of clinical presentation from the classical malabsorption to a number of non-GI presentations.  Some studies suggest that the frequency of celiac in a peds GI clinic is as high as 1:40 (general population is 1:130).  Presentations that are common other than diarrhea, distention or FTT include constipation, anemia, abdominal pain, intussception, vomiting, short stature abnormal LFT’s, pancreatitis, and asymptomatic detection upon screening.  30% of newly diagnosed patients are overweight.  There is about a 5% risk in 1st and 2nd degree relatives, patients with type I DM, Down syndrome, and thyroiditis.  In 300 pediatric patients over 9 years, 10% presented with diarrhea, 20% abdominal pain, 23% as a result of screening, 5% with constipation, and 26% with growth issues.  Rates in family members include 1st degree relative 5 – 10%, MZ twins – 75% concordance rate, DZ twins – 10% concordance rate and HLA identical sibs – 30% concordance rate.

Recommend: Think about celiac disease with a variety of GI symptoms including those present in overweight patients.  Screen asymptomatic patients with Down’s, William’s syndrome, Type I DM, Thyroiditis, and in patients who are family members of celiac patients.

2. How to Test

Serology: Under age 3 years (some say 2 years) there is consensus that to consider including antigliadin IgA and AGA IgG along with anti-TTG and quantitative IgA.  Over age 3, anti-TTG and quantitative IgA should suffice but many are recommending also ordering EMA.  There is good evidence that anti-TTG assays vary from lab to lab.  There is also good evidence that anti-TTG in an individual may fluctuate over time.  Patients in the Teddy study (The Environmental Determinants of Diabetes in the Young (TEDDY …) have had abnormal anti-TTG followed by normal levels on the next blood draw.  17/82 had a positive anti-TTG convert to a negative on a regular diet and remain negative at all follow-ups.  For purposes of the Teddy study, two consecutive abnormal anti-TTG over 0.5 should be the threshold for EGD.  EGD after one abnormal TTG in the asymptomatic screened individual, may be too soon and lead to a false sense of security.  In a patient on a GF diet, testing serology may still be useful if the GF diet is less than 6 months.  HLA typing may help rule out celiac in patients on GF diet.

Gluten exposure prior to biopsy: There is no consensus on how long a patient needs to be back on gluten before testing but most experts suggest at least a month and some 2 or more months.

Biopsy is still considered essential in confirming the diagnosis.  Some studies suggest that some patients (2 to 3% of kids and perhaps adults) may show abnormalities in the bulb but not in the 2nd or 3rd portion of the duodenum.

Recommend:  anti-TTG and IgA will catch most patients with celiac.  Under age 3, consider obtaining AGA IgG and AGA IgA.  Addition of EMA may increase sensitivity of the anti-TTG.  Biopsy is still considered by celiac experts to be essential for the diagnosis.  At least 6 duodenal biopsies are recommended.  Some recommend 4 additional biopsies from the duodenal bulb. HLA testing has a role (mostly in excluding the possibility of celiac) though there are rare patients (about 1 in 100 celiac patients though some report much less) that are DQ2 and DQ8 negative.  Not all labs test for the beta chain and this can lead to a false negative HLA DQ2.

3. When might scoping not be necessary?

There is no expert consensus on this. If serology and symptoms are highly suggestive of celiac in a patient with a first degree relative with celiac disease, it is reasonable to make a diagnosis without endoscopic exam.  To confirm diagnosis, it is helpful to see the antibody levels fall on a GF diet (usually retest after 6 months).  Some studies have shown lower compliance rates in patients without biopsy proven celiac.

Recommend:  It is a personal MD:patient:parent decision as to diagnosing celiac without a scope.  If you do diagnose without biopsy, make sure that serology improves on a GF diet.  Celiac centers standard of care still includes biopsy all newly diagnosed patients.
4.Treatment once the diagnosis is made

NIH consensus conference on celiac recommends:1) treatment include referral to a trained dietician (Atlantametroceliacs.com lists nutritionists for adults)  2) availability of a community support group – georgiarock.org or email to celiacgroup@ccdhc.org 3) follow-up with an MD experienced with celiac. 3) lifelong adherence to gluten-free diet 4) identification and treatment of nutritional deficiencies 4) follow-up with an MD familiar with celiac ideally as part of a multidisciplinary team (primarily in partnership with nutritionist).

Recommend:  All newly diagnosed patients or those struggling with compliance should see a specially trained dietician.  You can also refer to the ROCK group – georgiarock.org or celiacgroup@ccdhc.org  You should see the patient in follow-up after diagnosis.
5. Follow-up

Follow up frequency varies widely from every 3 months after initial diagnosis with a nutritionist and an MD to lesser intervals.  Once well controlled, many experts recommend annual visits, some every 2 years.  At diagnosis it is often recommended to look for deficiencies in iron, folate, vitamin D and B12.  Patients are also at risk for other fat soluble vitamin deficiencies and zinc deficiency.  Bone mineral density is often performed one year after diagnosis with abnormalities referred to endocrinology – recommendations in pediatrics are still in debate.  As patients with celiac are at substantial risk for other autoimmune disorders, it is worth considering thryoid problems (eg. check TSH and free T4) early on after diagnosis and once every 1 to 2 years though this practice is of debatable cost effectiveness.  It can take up to a year for the anti-TTG to normalize but it should be coming down significantly in 6 months.

Recommend:  At time of diagnosis, usually a CBC should be obtained to allow you to look for clues about iron, folate, and B12.  It is not unreasonable to check 25 OH Vitamin D levels as well.  At least yearly follow-up labs should include an anti-TTG but may also include TSH, free T4, Vitamin D and a CBC.  Screening for folate, B12, and iron deficiency may also be considered.  Follow up closely after diagnosis can be helpful in dealing with the stress of a major life change and to ensure compliance and understanding of the disease.

6. Testing family members

It is clear that 1st and 2nd degree family members – with and without symptoms are at high risk.  Offering to screen siblings and parents once a diagnosis is made is reasonable due to risks associated with celiac disease.  If an at risk patient screens negative with serology, it does not mean that they can not get celiac disease in the future.  Some experts recommend retesting every few years or sooner if there are symptoms.  It is important to document that you recommended screening to 1st degree relatives.

Recommend:  Strongly recommend that symptomatic first degree relatives be screened for celiac disease.  It is reasonable and helpful to offer to do the screening of parents and siblings yourself.  There is good data that it is important to screen asymptomatic people at risk as there are increased risks in adults of developing cancers, auto-immune conditions, anemia, and osteoporosis in untreated celiac disease.  There are no good recommendations for retesting at risk individuals who initially test negative. HLA typing, if negative, can be useful in eliminating the need for routine rescreening.

7. Feeding infant siblings

A multicenter trial is underway to try to determine the best time to introduce gluten to genetically at risk individuals.  There is good evidence that breast-feeding can be protective.  There is good evidence that introducing small amounts of gluten while still breast-feeding may be protective.  There is good evidence that introduction of gluten before four months of age may increase the risk of developing celiac.  Some evidence exists that the best practice is to give a teaspoon of a gluten containing cereal a few time a week between 4 and 6 months of age (Scandinavian data and prospective data out of the Denver diabetes trial).  Fassano suggests that there may be benefit in keeping the infant gluten-free for the 1st year of life and introduce while still brest feeding after a year of age.  Final answer is still pending.  Gluten can be found intact in human breast milk but not cow’s milk.  No recommendations regarding mother’s diet while breastfeeding a patient with or at risk of getting celiac are available.

Recommend: Do not introduce gluten to at risk infants before 4 moths of age.  Support breast-feeding as something that may delay or even prevent the development of celiac disease.  There is some data to suggest that tolerance may be more likely of small amounts (1 tsp a day) of gluten containing food are introduced between 4 and 6 months of age.  During breast-feeding, a mother who does not have celiac may eat gluten during the pregnancy and throughout infancy.

How helpful are probiotics?

Nobody really knows.  Claims about their efficacy are often based on poorly designed studies.  Efficacy of each strain for specific conditions and with specific dosing is often lacking.  One recent negative study demonstrates that probiotics are often not beneficial (J Pediatr 2012; 161: 40-3).

In this randomized, double-blind placebo controlled study of 106 Polish children (1-48 months of age), Lactobacillus reuteri had no effect in preventing nosocomial diarrhea in patients admitted for non-diarrheal illnesses.  While the authors contemplate that this could be due to the strain of probiotic chosen or the dose, it is clear that evidence that probiotics prevent infectious diarrhea “is still scant.”

This conclusion is backed by a large meta-analysis (JAMA 2012; 307: 1959-69).  While the study concludes that the use of probiotics is associated with a lower risk of antibiotic-associate diarrhea (RR 0.58), it predicted that the number to treat for one person to benefit would be 13.  The study was based on a systematic review of 82 randomized clinical studies.  Yet, overall the quality of the research was considered low; the studies were often had shortcomings:

  • 59 studies “lacked adequate information to assess the overall risk of bias”
  • 64 did not indicate if treatment randomization was blinded
  • 31 did not report an intent-to-treat analysis
  • 41 did not include a calculation of the study’s statistical power to detect differences
  • 17 trials were industry-sponsored and 52 did not clarify their funding/potential conflicts of interest
  • 59 did not report on adverse events specifically related to probiotic use; few trials addressed the risk of fungemia or sepsis
  • Trials rarely specified antibiotic agents; thus, it is difficult to know if a particular probiotic would be better with certain types of antibiotic therapy or duration.

Additional references/links:

  • Potential and pitfalls of probiotics with necrotizing enterocolitis
  • -JPGN 2010; 51:24. VSL#3 helpful for IBS, n=509 (4-18yr olds). 1 per day for <11yr, 2/day in 12-18yr olds
  • -Pediatrics 2008; 121:e850. Culturelle, during pregnancy and early infancy, not effective in preventing atopic dermatitis. Did increase wheezing.
  • -J Pediatr 2008; 152: 801. Probiotic helped reduce colic sx in 30 preterm infants, Lactobacillus reuteri
  • -Pediatrics 2007; 119; e124. Probiotics reduced colic in breastfed babies more than simethicone. n=83, Lactobacillus reuteri, 10-8th power per day. Decreased crying 18 minutes per day at 1 week compared to simethicone & by 94 minutes/day at 4 weeks (95% response vs 7% of simethicone)
  • -Neurogastroenterol Motili 2007 (Quigley EM, et al), 19: 166-72. Review of probiotics and IBS.
  • -NASPGHAN 2007, author: Brian Dunlap, H. Yu, Y Elitsur. abstract -most commercial yogurts have LOW concentrations of probiotics.
  • -JPGN 2006; 43: 550. Review of probiotics for specific conditions.
  • -J Pediatr 2006; 149: 367. Probiotics reduce risk of antibiotic assoc diarrhea. If 7 pts (on abx) are treated with probiotics, one fewer will develop AAD.
  • -JPGN 2006; 42: 454. Evidenced-based review of probiotics.
  • -Pediatrics 2005; 115: 1-4 & 171 editorial.  Probiotics decreased NEC in this study.
  • -Gastroenterol 2004; 126: 1620-33.  Review of probiotics, prebiotics and antibiotics in IBD.

Clues about constipation and more than 2.5 million views

A recent article identifies some important factors contributing to constipation in Hong Kong children (JPGN 2012; 55: 56-61).

Using a territory-wide questionnaire in 2318, Hong Kong Chinese elementary school students, the authors identified several factors associated with constipation which was present in 12.2% of this cohort:

  • Refusal to pass bowel movements at school (OR 1.97).  In Hong Kong, students spend >8 hours per day at school.
  • Having dinner with one/both parents <50% of time (OR 1.52).  May indicate less time with parents and less parental prompting.
  • Nighttime sleep <7 hours (OR 1.87).  This is postulated to be related to increased homework and more stress which may affect gut motility.
  • Frequent fast food consumption (OR 1.14).  This may be associated with less fiber intake.

On a tangential note, one of my sons informed me of “bad lip reading” on YouTube; some of these clips are really funny.  Since there was one relevant to the subject at hand, with over 2.5 million views, I’ve provided a link:

“Everybody Poops” – a bad lip reading of the Black Eyed Peas …

Additional blog entries related to constipation:

Stimulants for constipation

Diagnostic tests hardly ever help patients poop

It’s worth the cost

Think twice about checking thyroid

Best gastrostomy tube

A recent report touts the feasibility of a one-step percutaneous gastrojejunostomy (GJ) as the latest advance in enteral access (JPGN 2012; 54: 820-21).  This reference describes a new variation in technical placement: gastropexy using t-fasteners to secure gastrostomy tube site and then advancing neonatal scope via gastrostomy site to advance guidewire for  GJ placement.  This technique was used in three infants.

Most centers have developed their own protocols for enteral access and it is likely that the familiar approach to that center will be safest for their patient population.  Recently, the subject of gastrostomy tube placement was extensively reviewed in our institution (see below) due to variation in care at two children’s hospitals.  In one hospital, the surgical group primarily placed laparascopic button gastrostomies and argued that better visualization led to lower complications like colonic interposition.  Furthermore, this approach was considered similar in cost effectiveness as the group would place a primary Mic-Key® (http://www.mic-key.com/home.aspx) thereby eliminating the need for anesthesia for a button placement.

The alternative approach utilized a Corflo® gastrostomy tube (http://www.corpakmedsystems.com/product_main/enteral_main.html#FeedingTubes).  The advantages of this approach were 1) less anesthetic time/a smaller operation, and 2) lower likelihood of tube dislodgment.  This group approach argued that dislodgment was the greatest risk and that there was no urgency for a button tube.

Despite a joint meeting of these groups weighing the pros and cons, there was not a single best gastrostomy tube.

My experience is that tube dislodgment is quite common with button tubes.  In addition, primary button tubes can be difficult to size when the patient is under anesthesia.  As such, it is my practice to discourage primary gastrostomy button placement.  In addition, most patients who need gastrostomy tubes can wait until they are good surgical candidates both in terms of cardiorespiratory status and size.

Resources:

Gtube Products:
• AMT clamp –helps eliminate tubing pullouts
www.amtinnovation.com

• Gtube washable pads
www.oley.org  (specific web address: http://oley.org/lifeline/TubetalkJF11.html)

Additional references:

  • -J Pediatr 2011; 159: 602. Preemptive gtube assoc with improved survival post Norwood. High number needed fundoplication.
  • -JPGN 2011; 53: 293. 95% success with PEG in infants 2.1-5.6kg
  • -JPEN 2011; 35: 50-55. Predictive factors of mortality after PEG.
  • -JPGN 2009; 49: 237. Gtube improves height & weight in Rett syndrome.
  • -Clin Gastro & Hep 2007; 5: 1372. PEG placement does NOT prolong life in dementia patients.
  • -Arch Dis Child 2006; 91: 478-82. PEG reduced hospitalizations for respiratory dz in 57 severely impaired children
  • -J Pediatr 2006; 149: 837. inreased risk of PEG in SMA type 1 -42% w aspiration; 17% death (2/12)
  • -Pediatrics 2004; 114: 458-61. Moratlity rate of 0.4% -one death related to sepsis/peritonitis & 5% complication rate.
  • -Teitelbaum JE, Gorcey SA, Fox VL. Combined endoscopic cautery and clip closure of chronic gastrocutaneous fistulas. Gastrointest Endosc. 2005;62(3):432-435
  • -JPGN 2006; 43: 624. Satisfaction with PEGs: 94% of parents viewed PEG as positive influence on child’s situation & 98% would have chosen PEG insertion again (n=121).
  • -Sullivan PB, Dev Med Child Neurol 2005; 47: 77-83. 57 CP pts -almost all had improved health/nutrition p gtube
  • -Gastroenterology 2001; 121: 970-1001 & JPEN 2004; 28: S16. Provision of nutrition does not, for the most part, favorably alter clinical outcome.
  • -Lancet 2005; 365: 755-763. Pts c stroke/PEG did not do better than those c stroke/NGT.
  • -Sullivan PB, Dev Med Child Neurol 2004; 46: 796-800. gtube improves QOL.

Gastrostomy Tube Review with annotated references: Laparoscopic gtube versus conventional PEG placement

 Zamakhshary et al.  JPS 2005; 40: 859-62.   i.  Retrospective review, n=119 (only 26 with laparoscopy =21%). (2002-2003)  ii.  States same operative time of ~53 min by combining 2nd procedure w PEG (in 77% w PEG).  It takes these authors a long time to perform PEG and gtube change procedures.  Also, it is not noted how many of these 2nd procedures were coordinated with other needed anesthesias.  (Many times a PEG is replaced at the time of another procedure.)   iii.   3 PEG with transcolonic tube, 2 failed PEG –one with peritonitis, 4 with tract disruption when PEG pulled.  Similar rate of local problems (eg granulation tissue).  ARTICLE does not detail when PEG tubes are pulled –VERY high rate of tract disruptions.   iv. Article missing key details regarding size of PEGs & gtube buttons which may impact complications.  v. Cited advantages according to authors:

  1. “eliminates” risk of hollow viscus injury (JH: this is NOT  accurate)
  2. Useful for small infants (<2kg) (JH: usually gtube NOT needed in <2kg)
  3. Enables “ideal” location (JH: this is NOT  accurate)
  4. Primary button ‘advantage’ (JH: DOES NOT cite potential pitfalls like button too tight, possibility of balloon breakdown, possibly higher rate of dislodgment)

 Vervloessem et al. JPS 2009; 18: 93-97.     i. Retrospective review: 1992-2008.  N=467.  ONLY 19 Lap PEG –thus limited ability to provide comparison.  ii. Cites 59 “major complications” due to PEG –Table 2, including “13” new cases of GERD after PEG (or worsened GERD).  Of the major complications, important complications included 1 sepsis death, 7 peritonitis, 5 gastrocolic fistulas, 4 major granulation tissue, and 11 buried bumpers.  iii.  States that VPS is risk factor for infection but does not state whether any Lap gtubes were done in these patients.  iv. Complication rate decreased over the years—p=0.003; thus PEG procedure became safer with time and experience.   Could not demonstrate a decrease in complications with lap gtube versus PEG.  Authors recommend lap PEG in specific situations such as previous abdominal surgery or if not a good puncture site.

 Segal et al. JPGN 2001; 33: 495-500.    i. Retrospective study, n=110 (1990-97). N=110 –ALL PEG (no LAP). Thus, limited utility in comparing two methods. ii. “44%” developed late complications with PEG.  Most common: 24 extruded tubes/buried tubes (would NOT be better with lap button); other important: cologastric fistula n=2, peritonitis.  Table 1 indicates that 75% of dislodgment were due to buttons not PEG.  12 of the complications were granulation tissue and proliferative gastric mucosa.  Buried tubes occurred 14 & 19 months after placement with button tube!!   iii.  Thus this article adds little to the discussion of PEG vs lap gtube.

Akay et al. JPS 2010; 45: 1147-52  i.  Retrospective review (2004-2008) n=238 (134 PEG, 104 LAP)  ii. PEG with higher complications;  authors were changing PEG after 6-8 weeks. iii.  6 patients had early PEG dislodgment –this is higher than expected.  iv. 1 patient with gastrocolic-cutaneous fistula with both PEG & with LAP.  v. Table 4 lists complications: similar stomal issues, 2 patients with leak after PEG exchange (too early! –see page 1152) vi. Cited advantages: “eliminating” risk of hollow viscus injury, allows for sutures, small infants (<2kg) & possible primary buttons.**These authors did not place primary buttons –this makes it difficult to draw any conclusions about PEG vs primary LAP button.  Many feel PEG tube is a better tube and less prone to dislodgment than button and guarantees appropriate size.

Lantz et al. Int J Pediatr 2010; ID# 507616, 1-4.   i. Literature review, included 54 studies that qualified (1995-2009).  N=4331 (1027 LAP, 3304 PEG).  Very few details given in this review.  ii.Fistulas in 1.27% of PEG vs 0% for LAP.  iii.  Lists significant limitations: different studies, not blinded, nonpublication bias.  iv.  “This study highlights the need …for trials, comparing PEG to” LAP. v.  Does not include the limitation that LAP technique developed later and with more experience less complications.  Except for gastrocolic-cutaneous fistulas –no specific information is given about complications.

Avitsland et al.  JPGN 2006; 43: 624-28.  i. Restrospective review. N=121 –all PEGs  ii.     PEG “safe technique…major complications rare.”  “Most children experience minor stoma-related complications.”  iii. 29 died due to other factors.  Of 85 with f/u, 21 able to remove gastrostomy.  iv. No early mortality (<30 days).  1 of 85 had tube dislodgment.  3 had tube migration into esophagus (in cases where tube was not endoscopically removed).  v.     Frequent tube site problems ~75% -most easily treated. vi. Parents with high satisfaction: 83/85 (98%) would choose PEG again, 80/85 (94%) stated PEG improved child’s situation

Gauderer M. JPS 2001; 36: 217-19.   i.  Focused literature search and personal 20 year experience. ii. >216,000 PEGs performed annually in U.S. according to article (~5000 children).  PEG procedure developed 1st for children. iii.  Suggested approach to PEG with or w/o fundoplication: “Because PEG is such a simple procedure, a well-accepted approach is to place gastrostomy initially in children who can tolerate nasogastric tube feedings and add an antireflux procedure later, if needed.

Srinivasan et al. JPGN 2009; 49: 584-88.   i.Prospectively collected data from observational study, n=601 (384 PEG insertions, 165 button conversions).  ALL pediatric. ii.  Complications:  PEG site erythema 15%, buried bumper migration (1 patient), 3 PEG dislodgments, one patient had laparotomy due to severe pain (no findings identified).   No procedure-related mortality.   iii.  49 of 384 removed –no longer needed.  iv. “The role of PEG is well established…our experience..PEG has been generally safe, with low procedure-related morbidity in children.

Nutr Clin Pract 2005; 20 (6): 607-12.  Bankhead RR et al. i. Comparison of 91 patients.  23 PEG, 39 LAP, 29 open.  ii.   PEG had lowest complication rate

Surg Endosc 2006; 20: (8): 1248-51.  Ljungdahl M.                                         i.     Prospective, randomized study. N=70.  ii.  PEG with lower complication rate than surgical (open) gastrostomy –lower mortality & morbidity in adult patients.

UK Review Online: http://www.patient.co.uk/doctor/PEG-Feeding-Tubes-Indications-and-Management.htm   2009  i. Review of alternatives to PEG for gastrostomy insertion. There are alternative methods of gastrostomy tube insertion to PEG. They are: a) Laparoscopic insertion b) Open surgical technique c)Percutaneous radiologically guided gastrostomy (PRG) insertion. ii.  “There are reports over the years since introduction of PEG in the 1980s with often inconclusive results.21▪    A small study from Ireland and one from London favour PRG in patients with amyotrophic lateral sclerosis as it avoids the need for sedation or endoscopy.22,23▪  One meta-analysis suggested a higher success rate with PRG than with PEG, and less morbidity than either PEG or surgery.24 However a more recent comparison of a relatively small number of endoscopic, surgical and laparoscopic placement favoured PEG25 and another favoured PEG over PRG.26▪     A literature review suggested PEG as the procedure of choice for placement of gastrostomy tubes.27▪    A recent prospective randomized trial favoured PEG over surgical gastrostomy insertion.28▪     There is some evidence that polyurethane PEGs are less troublesome than silicone PEGs (less tube deterioration, less blockage).29▪    PEG is preferred in trauma patients.30▪                Antibiotic prophylaxis for PEG insertion appears to reduce the incidence of wound infection.19,20▪      Laparoscopic insertion was considered preferable to PEG by one study in children with PEG insertion having higher complication rate in children and often requiring repeat anaesthetics.31   An earlier study in children showed similar results for surgical, PRG and PEG insertion but did not look at the laparoscopic technique.32    A recent study from Norway found PEG insertion safe and very well tolerated by children and parents but made no comparison with other techniques.

Conclusions of review: PEG likely increases risk of gastrocolic fistulas (1-2%) but this has been reported with LAP as well.  The incidence is low.  No well-designed  studies have demonstrated superiority of LAP over PEG in terms of safety.  Potential drawbacks of LAP are likely underreported.  There have been cases of severe peritonitis at local hospitals following lap with primary gtube balloon misplacement.  Many feel PEG tube is a better tube and less prone to dislodgment than button (dislodgment is most frequent serious adverse event) and can be easily adjusted to  appropriate size.  To minimize complications, tube should not  be changed early.

Food choices, FODMAPs, and gluten haters

Given the frequency of functional gastrointestinal diseases (FGID), including irritable bowel syndrome (IBS), dietary treatments that may improve symptoms receive a lot of attention.  A recent review of the role of food choices in the development and management of FGIDs is a useful reference (Am J Gastroenterol 2012; 107: 657-66 -thanks to Ben Gold for forwarding this article).

This review details specific dietary advice as well as the following specific physiologic effects of FODMAPs:

  • Osmotic effects
  • Bacterial fermentation
  • Motility effects
  • Prebiotic effects
  • Systemic effects –mild depression, tiredness
In addition, the review looks at other potential foods which could serve as a trigger for IBS symptoms, like gluten & summarizes why some IBS patients are gluten haters.  The authors acknowledge that gluten sensitivity, in the absence of celiac disease, does not have a known mechanism.  Until a reliable marker becomes available, the importance of gluten sensitivity for FGIDs is unknown.
Related posts:

What to make of FODMAPs

Gluten sensitivity without celiac disease

Is a biopsy necessary in Celiac disease?

Save a life with free allergy education

Food allergy affects 4-8% of children and allergic reactions can be fatal.  In fact, the main cause of poor outcome with accidental food allergy exposure is delay in the use of epinephrine.  To improve parental knowledge and overall management of food allergies, a group of allergists, nurses and dieticians has developed and validated educational materials (J Pediatr 2012; 160: 651-6).  In addition, they have made these materials available at no cost online:

To validate their materials, the authors enrolled 60 parents of newly referred children with a prior food allergy.  The measured outcome was demonstration of an autoinjector for epinephrine.  The correct number of steps in the use of the autoinjector increased from a 3.4 to 5.95 score (max score 6).  In addition, at 1 year, the score remained high, 5.47.  Knowledge tests improved as well: from 9.2 to 12.4 (out of 15); at one year, the score was 12.7.  On a practical basis, the frequency of allergic reactions was reduced as well.  The annualized allergic reaction rate dropped from 1.77 (historical data) to 0.42 after the instruction.

The article also relates that some of the material relied on previous educational material, in particular the food allergy emergency plan available from the Food Allergy & Anaphylaxis Network (www.foodallergy.org).

Materials available include information on specific allergic disorders, avoiding allergens, management in and outside home, and living a safe/healthy life.  In addition, an educational video is available.

Additional references:

  • -Bock SA et al. J Allergy Clin Immunol 2007; 119: 1016-8. Poor outcome with accidental food allergy exposure is delay in the use of epinephrine.
  • -J Pediatr 2011; 158: 578.  Oral food challenges allowed 84% to return foods to diet.  n=125.
  • -Clin Gastro & Hep 2010; 8: 755.  Review of food allergy (vs intolerance) in adults.  Gives list of hypoallergenic diet , pg 758.
  • -Pediatrics 2009; 124: 1549-55.  3.9% of US kids w food allergy.  Nat’l surveys.
  • -NEJM 2008; 359: 1252 Review. Usual age of resolution: eggs  @ 7yr (75%), milk @ 5yr (76%); wheat/soy -rarely cause IgE-mediated allergies 80% resolve by 5yrs>  More  persistent allergens:  peanuts/tree nuts/sesame seeds = persistent in 80-90% at 5yrs, fish = persistent.
  • -Pediatrics 2003; 111: 1591-1680.  (supplement) Pediatric Good Allergy symposium
  • -Pediatrics 2003; 111:829-835. Infants c food-induced enterocolitis often have multiple food allergies (cereal, veggie, poultry, meat)  IgE based tests are negative (skin prick & IgE Abs
  • -Gastroenterology 2001; 120: 1023-25; 1026-40.  AGA position paper; technical review.
  • -J Allergy Clin Immmunol 1999; 103: 717-728 &981-9.  Pathogenesis &  Dx/ mgt.

VTE with IBD

In our children’s hospital, work is underway to systematically screen children for risk factors for venous thromboembolism (VTE) and to establish an algorithm to lower the risk of a VTE with either mechanical or pharmacologic treatments. One of the risk factors has been the presence of inflammatory bowel disease (IBD).  The absolute risk of IBD for VTE is not clear.  However, a recent study relates the risk among a large Danish population of adults and children (Gut 2011; 60: 937-43).

The study included 49,799 patients with IBD (14,211 Crohn’s, 35,229 UC) and compared with 477,504 members of the general population.  VTE risk for IBD was increased with HR of 2.0.  The incidence of VTE increased with age; however, the RR was higher in younger patients.  Among those less than 20 years, HR was 6.6 for VTE; HR 6.0 for DVT and 6.4 for PE.  In this age group, “unprovoked” VTE had HR of 4.5.  Unprovoked VTE was defined as event occurring without malignancy, recent surgery, pregnancy or fracture.

Although the relative risk is increased, the authors caution that the absolute risk in younger patients is low.  In those IBD patients less than 20 years, the incidence rate was 8.9 per 10,000 person years.  In contrast, in those IBD patients older than 60, the incidence rate was 54.6 per 10,000 person years.  There did not seem to be a significant difference between Crohn’s disease and ulcerative colitis in absolute or relative risk. The authors conclude that in those IBD patients younger than 20 years without ‘other VTE risk factors or limited mobility, the benefits of prophylaxis may no longer outweigh the risks.”  In older patients (>60 years), even outpatients experiencing flares might benefit from VTE prophylaxis.

Additional references:

  • -NEJM 2012; 366: 860 (letter to editor). Authors emphasize importance of VTE with UC, especially during flares.
  • -Lancet 2010; 375: 657-63. VTE with active IBD and in remission.
  • -Clin Gastroenterol Hepatol 2008; 6: 41-5. Thrombosis with IBD.
  • -Gut 2004; 53: 542-8. IBD -risk factor for VTE?
  • -Gut 2004; 53 (suppl 5): v1-16. IBD guidelines for management.

More on PNAC

In a previous blog entry (PNAC, PNALD, and IFAC), reduction in intralipids was shown to improve parenteral nutrition associated cholestasis (PNAC).  This change in the use of parenteral nutrition (PN) and others are emphasized in a review article by the American Pediatric Surgical Association (J Ped Surg 2012; 47: 225-40).

This review tries to provide evidence-based guidelines for PNAC with ratings of the evidence for each of their recommendations.

A summary of their findings is given in Figure 1 of the article.  Key points:

  • PN duration is a significant predictor for cholestasis
  • NEC & sepsis both play a role in the development of PNAC
  • Insufficient data to determine if antibiotics used to decrease bacterial translocation/hepatocyte damage may be beneficial
  • Fat emulsion restriction may reduce PNAC without detriment to growth
  • Fish-oil based lipid emulsions are safe and effective for PNAC.  “Despite the promise of Omegaven…the literature is insufficient to provide a recommendation higher than grade C.”  (Grade C= “possibly effective, ineffective, or harmful;” requires at least 2 convincing class III studies [class III studies generally are non-randomized non-blinded studies]).  Information to obtain Omegaven:

http://www.oley.org/documents/How_Physicians_Can_Obtain_Omegaven.pdf
http://www.oley.org/lifeline/PN_Liver_Disease.html

  • Strong evidence that higher initial protein load does not increase the risk of PNAC
  • Strong evidence that trophic feeds are beneficial to reduce PNAC
  • Weak/conflicting evidence that there is any benefit of Aminosyn over Trophamine
  • Weak evidence to support the routine removal of copper or manganese from PN as a prophylactic strategy to prevent PNAC
  • Weak evidence to support prophylactic cycling of PN to reduce PNAC.  There are also concerns about the development of hypoglycemia in preterm infants off of PN
  • Use of CCK is not recommended
  • Oral bile acids may result in improvement
  • Erythromycin may promote motility and facilitate enteral feeds, thereby reducing PNAC

Common to be “D-ficient”

Many of the children that a pediatric gastroenterologist sees are at risk for Vitamin D deficiency, including children with inflammatory bowel disease, cystic fibrosis, celiac disease, and liver diseases.  In addition, vitamin D deficiency is widespread: in U.S. 50% of children aged 1-5 years and 70% 6-11 years are vitamin D deficient or insufficient. A thorough review on this “D-lightful” vitamin was in a recent JPEN (JPEN J Parenter Enteral Nutr 2012; 9S-19S).

History: In 1822 Sniadecki recognized children in urban but not rural Poland developed rickets. He postulated the effects of the sun as the reason for rickets; his idea was dismissed.  In 1920s, the concept of irradiating milk to prevent rickets emerged. In 1950s, outbreak of hypercalcemia in infants in Great Britain was thought to be related to vitamin D fortification and curtailed this practice in Europe.  However, these cases were likely due to Williams syndrome.

Sources of vitamin D: oily fish (salmon), cod liver oil, some mushrooms, egg yolk, & sunlight. Exposure of an adult in a bathing suit to one minimal erythemal dose (MED) is equivalent to ingesting 20,000 IUs of Vitamin D. (The minimal dose that induces any visible reddening at that point is defined as one MED.)

Effect of sunscreen: A sun protection factor (SPF) of 30 absorbs approximately 98% of solar ultaviolet radiation & thus lowers vitamin D production by 98%.

Ethnicity: Melanin is an effective SPF.  A person of african-american descent, on average, has an SPF of 15, which reduces vitamin D production by 90%.

Age: Aging decreases 7-dehydrocholesterol in human skin.  Due to this, the elderly produce much less vitamin D.  For example, a 70 year old has a 75% reduction compared to a 20 year old.

Forms of vitamin D:  25-hydroxyvitamin D (25OH-D) is the major circulating form of vitamin D & physicians measure 25OH-D. 25OH-D is metabolized in kidney to 1,25-dihydroxyvitamin D (1,25OH-D), also called calcitriol.  This is the most biologically-active and is responsible for increasing intestinal calcium absorption and mobilizing calcium from bone.  However, 1,25OH-D provides no information vitamin D deficiency; it can be elevated or normal in deficiency states.

  • Cholecalciferol (vitamin D-3) is formed in the skin from 5-dihydrotachysterol.
  • Ergocalciferol (Vitamin D-2) is the form in Drisdol (8000 IU/mL) & Ergocalciferol Capsules (1.25 mg =50,000 USP Units)

Vitamin D deficiency:  The exact numbers are debated.  The institute of medicine (IOM) has considered individuals deficient if 25OH-D is <20 ng/mL.  The Endocrine Society and the author suggest vitamin D deficiency as <20 ng/mL & insufficiency as <30 ng/mL.  The author recommends ideal levels between 40-60 ng/mL.

Consequences of deficiency:

Osteoporosis, Osteopenia, Rickets (see references below): Bone weakening occurs due to loss of phosphorus from the kidneys.  Vitamin D deficiency lowers accrual of calcium in skeleton and leads to osteoporosis, osteopenia, and rickets. Imaging for rickets: the best single radiographic view for infants and children younger than 3 years is an anterior view of the knee that reveals the metaphyseal end and epiphysis of the femur and tibia. This site is best because growth is most rapid in this location, thus the changes are accentuated.

Nonskeletal consequences: vitamin D deficiency is associated with increased risk for preeclampsia, URIs, asthma, diabetes (type 1), multiple sclerosis, hypertension, and schizophrenia.

Treatment:

  • Infants who are breastfed should be receiving supplemental vitamin D, 400 IU/day.
  • Adults/children (>1 year) RDA 600 IU/day –mostly from diet per IOM. Yet author states, “it is unrealistic to believe that diet alone can ….provide this requirement.”
  • In vitamin D deficient patients: (initial treatment) 2000 IU/day or 50,000 IU/week for 6 weeks.
Toxicity from vitamin D (from NEJM 2010; 364: 248-254.): “Toxicity from vitamin D supplementation is rare and consists principally of acute hypercalcemia, which usually results from doses that exceed 10,000 IU per day; associated serum levels of 25-hydroxyvitamin D are well above 150 ng per milliliter (375 nmol per liter). The tolerable upper level of daily vitamin D intake recently set by the Institute of Medicine (IOM) is 4000 IU.”

Additional references:

  • -Pediatrics 2008; 122: 398. Should give 400 IU/day to breastfed babies. Consequences of Vit D deficiency: increased risk for DM, multiple sclerosis, cancer (breast, prostate,colon), rickets, and schizophrenia. Article lists vit D content of foods (high in cod liver oil, shrimp, fortified milk, many fish). Severe deficiency when < 5ng/mL, deficient if < 15 ng/mL; probably should be >32 ng/mL. Causes of vit D deficiency: decreased synthesis (due to lack of sun -skin pigmentation, sunscreen/clothing, geography, clouds), decreased intake, decreased maternal stores & breastfeeding, malabsorption (eg celiac, CF, EHBA, cholestasis), increased degradation; treatment of rickets: double-dose of vitamin d (~1000 IU/day for babies & 5000 for older kids) x 3-4 months along with calcium (30-75/mg/kg/day). Follow Ca/phos/alk phos monthly. Alternatively, give ~100,000 units over 1-5 days.
  • -JPEN J Parenter Enteral Nutr. 2011;35:308-316-Results: The study included 504 IBD patients (403 Crohn’s disease [CD] and 101 ulcerative colitis [UC]) who had a mean disease duration of 15.5 years in CD patients and 10.9 years in UC patients; 49.8% were vitamin D deficient, with 10.9% having severe deficiency. Vitamin D deficiency was associated with lower HRQOL (regression coefficient –2.21, 95% confidence interval [CI], –4.10 to –0.33) in CD but not UC (regression coefficient 0.41, 95% CI, –2.91 to 3.73). Vitamin D deficiency was also associated with increased disease activity in CD (regression coefficient 1.07, 95% CI, 0.43 to 1.71). Conclusions: Vitamin D deficiency is common in IBD and is independently associated with lower HRQOL and greater disease activity in CD. There is a need for prospective studies to assess this correlation and examine the impact of vitamin D supplementation on disease course.
  • -JPGN 2011;53: 361. similar prevalence of low Vitamin D as general population –58% with less than 32.
  • -JPGN 2011; 53: 11. Guidelines for bone disease with inflammatory bowel disease.
  • -Pediatrics 2010; 125: 633. Increasing Vit D deficiency noted in minority children. n=290. 22% w levels <20, 74% <30.
  • -Hepatology 2011; 53: 1118. Good vitamin D levels are another favorable predictive factor in antiviral response to Hep C along with IL28B.
  • -NEJM 2010; 364: 248-254. Vitamin D insufficiency. Levels between 20-30 may be OK -not enough evidence to determine conclusively whether this level is detrimental
  • -J Pediatr 2010; 156: 948. High rate among african americans with asthma, 86%. n=63.
  • -Pediatrics 2009; 124:e362. n=6275. 9% of pediatric patients vit D deficient & 61% were insufficient.
  • -Pediatrics 2009; 124:e371. n=3577. low 25OH-D levels inversely assoc with SBP/metabolic syndrome.
  • -NEJM 2009; 360: 398. case report of rickets
  • -J Pediatr 2003; 143: 422 & 434
  • -Pediatrics 2003; 111: 908. 200 IU Vit D recommended for all breastfed infants.
  • -J Pediatr 2000;137: 153 & 143.. Nutritional rickets–primarily in blacks; rec vitamin D 400 IU per day.