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GIKids Resource

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For those of you who have not visited GIKids.org website:

GIKids – A Resource for Pediatric Digestive Disorders

It has literally A-Z handouts on pediatric GI problems for families, including four new handouts:

Educated or Misinformed –Leading to Hemorrhagic Disease of the Newborn

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“Hemorrhagic Disease of the Newborn,” now termed “Vitamin K Deficient Bleeding,” has reemerged as a problem. Many well-intentioned parents are refusing vitamin K to keep things more ‘natural’ for their infants.  This phenomenon is likely encouraged by some alternative health websites and other parents; babies who are breastfed are at increased risk of vitamin K deficiency (without prophylaxis).  Unfortunately, they are playing Russian roulette with their infant’s safety. In addition, many practitioners will not readily recognize this disorder because of the effectiveness of Vitamin K prophylaxis that has been provided since 1961.

An excerpt from the St. Louis Dispatch provides more information: Four babies hemorrhage after parents refuse vitamin K shot, a practice on the rise

Maternity care providers here and nationwide are on high alert for life-threatening vitamin K deficiencies in newborns, at the same time they are seeing more parents refusing a routine preventive injection.

The Centers for Disease Control and Prevention released a report last month about four babies in Nashville, Tenn., who hemorrhaged after their parents refused vitamin K injections at birth. The babies were diagnosed with life-threatening vitamin K deficiency bleeding between February and September. Three had bleeding in the brain, and one had gastrointestinal bleeding. They survived, but the infants with brain hemorrhages could have long-term neurological problems.

“Not giving vitamin K at birth is an emerging trend that can have devastating outcomes for infants and their families,” CDC director Dr. Tom Frieden stated in the report. “Ensuring that every newborn receives a vitamin K injection at birth is critical to protect infants.”

The vitamin is necessary for normal blood clotting, but because vitamin K does not transfer well across the placenta, most babies are born with low levels. The deficiency can lead to a rare, sudden bleeding disorder up to 6 months of age.

The CDC investigation found that parents refused the injection for several reasons, including a concern about an increased risk for cancer from the injection, an impression that it was unnecessary and a desire to minimize exposure to “toxins.” A 1992 study associated vitamin K and childhood leukemia, but the findings have been debunked by subsequent studies…

The number of parents refusing is more alarming at birth centers, which provide care led by midwives who support natural birth. Among the most recent 75 births at the Birth and Wellness Center in O’Fallon, Mo., 23 percent refused the injection, and 14 percent opted for the oral dose, said Jessica Henman, the center’s certified nurse midwife.

The CDC studied a random sample of births this year in the Nashville, Tenn., area and found that parents of 3.4 percent of 3,080 newborns discharged from hospitals had refused the vitamin K injection, while parents of 28 percent of 218 born at birth centers had refused…

A newborn not getting the injection is 81 times more likely to get the late form of the disorder than a baby who gets the shot, according to the CDC. [my emphasis in bold]

Related link from Stanford:  Guidelines for Vitamin K Prophylaxis – Newborn Nursery at LPCH

Bottomline: When seeing an infant with bleeding, ask about vitamin K prophylaxis after birth.

If a parent caused intracranial hemorrhage in an infant by shaking the infant, they would probably be jailed.  What should be done in these cases?

Related blog post:

Bleeding due to vitamin K deficiency | gutsandgrowth

Something New with FMT

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“Resentment is like drinking poison and then hoping it will kill your enemies.” –Nelson Mandela

A brief review on Fecal Microbiota Transplantation (FMT) (Gastroenterol 2013; 145: 946-53) made a few points that I was not familiar with and reiterated many other important aspects.

  • With regard to preparation of FMT, early data suggests that using water rather than saline may result in better resolution of Clostridium difficile infection (CDI)
  • Adequate volumes of FMT material are needed, with rates as high as 97% CDI resolution with infusions >500 mL
  • While preliminary data suggested higher CDI resolution with colonoscopy infusion, a recent randomized controlled trial indicated that duodenal infusion was as effective as colonoscopic administration
  • Short-term data indicate very low adverse effect rates
  • While the only accepted role for FMT outside of clinical trials is for CDI, the review examined the potential benefit for inflammatory bowel disease (IBD), irritable bowel syndrome, chronic fatigue syndrome, and metabolic/cardiovascular disorders.
  • With IBD, there are currently 6 registered trials testing FMT for patients with IBD.  Preliminary data have been more evident in small studies with ulcerative colitis.
  • The rationale for FMT in IBD is that IBD patients have reduced diversity and altered microbial flora.  “However, it is not clear whether these differences are a cause or a consequence of the development of IBD.”

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Fiber Intake and Crohn’s Disease

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There are several lines of evidence that diet can contribute to the development and treatment of Crohn’s disease.

From a treatment standpoint, the most dramatic data has been with the effectiveness of enteral nutrition as a treatment option.  In addition other environmental factors like being raised on a farm and use of antibiotics have been shown to alter the risk for Crohn’s disease; the former has been associated with a reduction in risk and the latter with an increased risk.

A new prospective study from 170,776 women followed over 26 years in the Nurses’ Health Study has identified up to a 40% reduction in the risk of Crohn’s disease among the highest fiber intake quintile (24 g/day) in comparison to the lowest intake quintile (12 g/day) (Gastroenterol 2013; 145: 970-77, editorial 925).  Link to abstract: http://dx.doi.org/10.1053/j.gastro.2013.07.050 …

Specific findings:

  • Fruit intake was associated with greatest risk reduction.  The median daily intake of fiber from fruit in the highest quintile was 6 g/day which is equivalent to 2 fruits (eg. banana or orange).
  • Vegetable intake was not associated with protection from Crohn’s disease.
  • The editorial notes that “reverse causation was addressed by evaluating cumulative exposure and including a 2-4 year lag period.”
  • However, the women in this study may not be representative and fiber intake could be an epiphenomenon.  The women in the highest quintile were also less likely to smoke, use aspirin and have a body mass index <30 kg/m-squared.
  • Fiber intake did not significantly reduce the risk of ulcerative colitis

Bottomline: the “Institute of Medicine recommends that daily fiber consumption should be 14 g of fiber for every 1000 calories.”  Thus, if one were to follow the guidelines by the IOM, all individuals would be consuming enough fiber to potentially reduce their risk of Crohn’s disease by 40%.  Other fiber benefits include improve bowel habits, lowered cholesterol levels, weight loss, and lowered diabetes risk.

Related blog links:

Also, in the past week, I posted a blog regarging Hepatitis C (Wiping out Hepatitis C | gutsandgrowth).  Another helpful review of the emergence of new therapies comes from yesterday’s NPR.  This story also reported that the expected (not yet set) cost of sofusbuvir will be $90,000!  Here’s the link:

http://www.npr.org/blogs/health/2013/12/05/248934833/fda-set-to-approve-hepatitis-drug

 

Reporting Bias: Infections with TNF Inhibitors

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A recent article (Clin Infect Dis 2013; 57: 1318-30 -thanks to Jeff Lewis for this reference) summarized the pediatric literature on infectious complications associated with tumor necrosis factor-α (TNF) inhibitors for both Juvenile Idiopathic Arthritis (JIA) and Inflammatory Bowel Disease (IBD).

In total 33 studies for JIA were included and 39 studies for IBD.  Many others were excluded due to overlapping cohorts or lack of sufficient data.

For JIA, the authors identified 296 infliximab (IFX) patients, 2465 etanercept patients, and 242 adalimumab patients.  Most infectious were mild and mainly viral etiology.  For example, 1016 upper respiratory illnesses with etanercept were reported.  However there were a significant number of more serious infections which included lower respiratory infections (n=37), cellulitis/abscess (n=15), histoplasmosis (n=2), and meningitis (n=4). Four patients had infectious fatalities.

Similarly, for IBD, most patients had mild infections.  Among 1407 IFX patients and 241 adalimumab (ADA) patients, there were 105 URIs noted.  Again, more serious infectious were noted in many.  Four fatalities were reported; 1 was due to disseminated CMV, 1 due to bacterial sepsis, and 2 were due to central line infections.

When examining this report, the question of reporting bias cannot be avoided. The various reports that were summarized included 30 prospective studies, 23 retrospective studies, and 19 various reports (case reports, case series, and FDA reports).  The composite, in my view, likely overestimates the risk of serious infections.  In addition, many of the infections may have been due to concurrent immunosuppressive therapy, but the details for this are lacking.

With regard to microbiology:

  • 5 JIA patients had tuberculosis; there were no tuberculosis cases reported in the IBD cohort
  • Varicella/zoster was the most frequent viral infection and was frequently severe.  In JIA cohort, there were 39 VZV cases (11 severe); among IBD cohort, there were 16 VZV cases (3 severe).

Bottomline: Given the frequent use of anti-TNF agents, better prospective pediatric data are needed.  In addition, careful analysis of the data is needed for better attribution; the risk for many of these infections is likely due to concurrent medications like corticosteroids.

Also Noted:

Clin Gastroenterol Hepatol 2013; 11: 826-31.  In a prospective cohort of 200 anti-TNF-naive adult patients (100 treated with IFX and 100 with ADA), the effectiveness was similar for IFX and ADA at both 1 and 2 year followup.  Improved efficacy was noted when these agents were combined with immunomodulators, though this was statistically significant for IFX. The total patient response was 63.5% at 1 year and 45% at 2 years.

Related posts:

Rehabilitation for Short Bowel Syndrome

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As noted in several blog posts, there have been some important advances in the care of short bowel syndrome (SBS)/intestinal failure (IF) patients which have resulted in improved outcomes.  A recent review of 28 children with ≤20 cm of small bowel has been published (J Pediatr 2013; 163: 1361-6, editorial 1243) and provides tangible evidence of these changes.

This retrospective study reviewed the charts of these children managed at Omaha’s intestinal rehabilitation program.  7 patients had NEC, 6 intestinal atresia, 6 had gastroschisis, 3 omphalocele, 5 had malrotation, and 1 patient had vascular disease.

Key results:

  • 27 survived (96%)
  • 14 (50%) had at least one lengthening procedure; in this cohort, bowel lengthening was not associated with a greater rate of adaptation than native bowel.
  • 13/27 (48%) achieved parenteral nutrition independence (“nutritional autonomy”) with their native bowel.
  • Predictors of “successfully rehabilitated” patients: intact colon and ileocecal valve
  • All patients had improvements in lowering PN requirements, total bilirubin, and growth z-scores.
  • Serum transaminase levels did not improve in the nonrehabilitated patients

The main medical treatments at IRP include use of agents for control of bacterial overgrowth, reducing gastric acid production, lipid minimization, promotility and antimotility agents (eg. loperamide), and ethanol locks.  The editorial comments on the “poor results” for surgical intervention, “particularly among those with ultra-short bowel.” This may be due to ‘marginal motility, ischemia, severe wall thickening, or due to adhesions.’

With regard to ethanol locks, the editorial supports them but states, “the main factor in prevention [of line infections] has been maintaining a consistent and strict protocol for catheter care.”

Previous related blog entries:

How Birth Can Affect Your GI Tract

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A recent review (JPGN 2013; 57: 543-49) provides information about the relationship between neonatal environment and subsequent inflammatory gastrointestinal disease.

While most of the review, focuses on physiology and pathophysiology, the most interesting part is the assertions (with references) in Table 1 which include the following:

  • Breastfeeding reduces risk of IBD
  • Cesarean section increases the risk of celiac disease, cow’s milk allergy, and other IgE-mediated food allergies
  • Many chronic adult diseases have been shown to have origins in neonatal life, particularly cardiovascular disease/metabolic syndrome

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Primary Enteric Nervous System Disorders

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If you are wondering what these are, you may want to review a recent consensus statement (JPGN 2013; 57: 677-86).

This ‘practical guide’ discusses Hirschsprung’s disease, intestinal neuronal dysplasia, chronic intestinal pseudo-obstruction, ultrashort segment Hirschsprung’s disease, hypoganglionosis, and ganglioneuromatosis in MEN 2B.

Most of the focus is on Hirschsprung’s disease including the intricacies of diagnosis, clinical presentation, and genetics.  While the authors do mention the PHOX2B gene and others, there is not a discussion of Ondine’s curse (Congenital central hypoventilation syndrome and Hirschsprung’s …).  One point that I think is important (but not discussed in the above reference) in patients who have Ondine’s curse and Hirschsprung’s is determining whether a family member may have a milder phenotype that could still place them at risk for sudden death (eg. after a simple sedation procedure).

Related blog post:

What is calretinin? | gutsandgrowth

Explaining the Vitamin D Paradox

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For a long time, there has not been a satisfying explanation for the fact that blacks have higher bone mineral density but lower 25-hydroxy-vitamin D levels than whites.  New research (NEJM 2013; 369: 1991-2000, editorial 22047-48) helps explain this paradox.

This study examined a community cohort of 2085 individuals in the “Healthy Aging in Neighborhoods of Diversity across the Life Span” study.

Key Findings:

  • Blacks had higher bone mineral density and lower 25-hydroxy-vitamin D levels than whites
  • The calculated bioavailable levels of 25-hydroxy-vitamin D were similar to whites.

The editorial notes that the similar bioavailability is due to differences in the vitamin D-binding protein (aka GC-globulin).  “GC1F is the most abundant form in persons of African ancestry whereas GC1S is most abundant in European populations.”  Thus, it has been hypothesized that the vitamin D-binding protein in blacks has “increased affinity for vitamin D3, and thus able to transport vitamin D3 more efficiently from the skin to the liver for its metabolism to 25-hydroxy-vitamin D.”

Bottomline: This research in vitamin D metabolism may impact on how we determine vitamin D deficiency.  The measurement of vitamin D-binding protein may need to be incorporated into the assessment.

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Reclassifying Biliary Atresia -Three Subtypes

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Using a large prospective multicenter cohort (ChiLREN study group), a recent study examined 289 infants and identified three subtypes of biliary atresia (BA) enrolled in PROBE (Hepatology 2013; 58: 1724-31).

Previously, BA has been considered to have two presentations:

  • Acquired/nonsyndromic ~90%
  • Embryonic/syndromic ~10%

However, this study suggests the following:

  • Group 1 -nonsyndromic, isolated BA. n=242 (84%)
  • Group 2 -BA with major malformation but without laterality defect. n=17 (6%)
  • Group 3 -syndromic, with laterality defect. n=30 (10%)

Group 3 BA defects included splenic abnormalities (eg. asplenia, polysplenia, right-sided spleen), cardiovascular anomalies (eg. dextrocardia, TAPVR, interrupted IVC) and gastrointestinal anomalies (eg. “abdominal heterotaxy,” malrotation, annular pancreas).

In contrast, Group 2 BA had frequent genitourinary problems (cystic kidney and hydronephrosis) along with different cardiovascular anomalies and gastrointestinal anomalies which included esophageal/duodenal/jejunal atresia and imperforate anus.

Other points:

  • The frequency of cardiac problems is particularly important to recognize as this could make differentiation from Alagille syndrome more difficult.
  • One other interesting finding was the high incidence of autoimmunity in first-degree relatives of all BA groups (~44%).

Bottomline: there are at least 3 subtypes of BA.

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