Tag Archives: necrotizing enterocolitis

Green beans for short gut syndrome

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A recent article indicates that the addition of green beans may improve diarrhea and reduce dependence on parenteral nutrition (Adding Dietary Green Beans to Formula Resolves the Diarrhea …) (ICAN. DOI: 10.1177/1941406412469403). Thanks to Kipp Ellsworth for pointing out this reference on his twitter feed.

This small retrospective study of 18 infants examined the addition of green beans to the diet of infants with short bowel syndrome (SBS) (1 jar of stage 2 baby food green beans to every 8 ounces of 30 cal formula).  The average gestational age of the patients was 32 weeks (range 23-39 weeks) and the average birth weight was 1938 gram.  Nine patients had NEC, four had gastroschisis, two had Christmas tree defect, and three had other reasons for either SBS or intestinal failure.  The IF group (n=10) was defined as being dependent on parenteral nutrition to meet nutritional needs; the SBS group (n=8), who were more severely affected, was defined as the malabsorptive state that follows a massive resection.

Products that were used:

  • Gerber Natural Select: 3 gm of fiber per 4 ounce
  • Beach-Nut Homestyle: 2 gm of fiber per 4 ounce
  • HyVee Mother Choice: 2 gm of fiber per 4 ounce
  • These products average 32% soluble and 68% insoluble fiber

While the authors note that they use only amino-acid based formulas currently, at the time of the study, 61% were receiving Peptamen Junior.

It is not clear in the manuscript exactly at what age green beans are introduced. However, a previous case study suggested addition of green beans at ~4 months or >44 weeks postconception.  This prior case study indicated that adding stage 2 green beans changed the caloric density of 30 cal formula to 22 cal/ounce (Nutrition in Clinical Practice 2005; 20: 674-77).  In addition, this adds 2 gm/kg/day of fiber.

Results from current study:

  • 9 of 10 IF patients were able to discontinue parenteral nutrition
  • 2 of 8 SBS patients were able to discontinue parenteral nutrition
  • All infants had improvements in stool consistency, typically within 24 hours of dietary change.

While the authors acknowledge the limitations of the study, they hypothesize that the reason for improvement is due to the fiber content of green beans.   Fermentation of dietary fiber produces short chain fatty acids (SCFAs) which in turn have a trophic effect on the mucosa and enhance nutrient absorption.

Studies have shown that adults with IF or SBS have improved stool consistency with the addition of fiber.  However, the authors note that there have been no studies documenting the effectiveness of dietary fiber in the pediatric SBS/IF population.

Whether green beans would outperform other sources of fiber like pectin, guar gum, bananas or benefiber is not clear.

Additional references/links:

Predicting Necrotizing Enterocolitis with Fecal Biomarker

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A recent study has shown some promise in detecting necrotizing enterocolitis (NEC) with a fecal biomarker, S100A12 (J Pediatr 2012; 161: 1059-64).

In this prospective study of 145 preterm infants with a birth weight <1500 g, stool samples were collected on alternated days for 4 weeks.  Fecal S100A12 and calprotectin were measured.  Calprotectin in previous studies has been shown to be a poor marker for NEC.

Fecal S100A12, also called calgranulin C, belongs to a novel group of proinflammatory molecules. It is released by activated or damaged cells under conditions of cell stress and indicates phagocyte-specific damage.

18 (12.4%) developed NEC.  Fecal S100A12 levels were elevated in severe NEC and also at 4-10 days beforehand.  The sensitivity, specificity, positive predictive values, and negative predictive values were 70%, 68%. 37%, and 89% respectively.  Thus, there is limited utility of this stool test due to the limited sensitivity/specificity.  There is substantial overlap between control patients and patients who developed NEC.  Furthermore, fecal S100A12 levels are age-dependent.  Generally, they are higher early in life, likely due to increased mucosal permeability.

Calprotectin levels were elevated at the onset of NEC (median 349 mg/kg) and 48 hours before onset (median 83 mg/kg).  The difference at 48 hours prior to onset did not reach statistical significance.

NEC and thickening agents

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Last year the FDA issued a warning regarding food thickeners and necrotizing enterocolitis (FDA: Do not feed SimplyThick to premature infants).  More details are now available (J Pediatr 2012; 161: 354-6).

This information was derived from a series of cases of NEC with a common antecedent, the use of SimplyThick.  After excluding infants with multiple episodes of NEC prior to use of this thickening agent, 22 infants met the case definition and were included in the report.

16 infants started SimplyThick >37 weeks post-menstrual age (PMA).  19 infants developed NEC >37 weeks PMA.  14 cases required surgery and 7 patients died.  The number of days of SimplyThick exposure:

  • 9 patients  –1-10 days
  • 7 patients –11-20 days
  • 6 patients –>20 days
  • Median –13 days

Since most cases of NEC occur in the hospital and are associated with extreme prematurity, these cases are unusual & likely causally related to the use of SimplyThick.  Delayed NEC can also occur with congenital heart disease.  Also, NEC often develops shortly after the introduction of enteral feedings; in this series, patients had been receiving enteral feeds for a median of 43 days prior to NEC onset.  As a consequence, 50% of patients were at home when NEC developed.

The authors postulated that an increased production of short-chain fatty acids by breakdown of xanthan gum component was the mechanism for SimplyThick to increase the risk of NEC.

In a brief commentary on the article, Alan Jobe states that “Neonatologists seem determined to treat the poorly defined reflux that frequently occurs in preterm infants with something –preferably drugs that are off-label and have no proven efficacy…Perhaps clinicians should restrain their enthusiasm for other thickeners for the feeding of preterm infants as well.  The proven treatments for reflux in otherwise normal preterm infants are time and patience.”

While Dr. Jobe makes some helpful points, SimplyThick has been used primarily for swallow dysfunction rather than reflux.  Nevertheless, any thickeners as well as reflux medications can increase the risk of NEC and should be used cautiously.

Related posts:

Avoid ranitidine (acid suppression) in neonates

Do medicines work for GERD infants?

Avoid ranitidine (acid suppression) in neonates

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More evidence that ranitidine may contribute to necrotizing enterocolitis and fatal outcomes has been published (Pediatrics 2012; 129: e40-45).

In this study (which was reviewed in The Journal of Pediatrics 2012; 161: 168-69), four neonatal intensive care units in Italy performed a multicenter prospective observational study of very low birth weight (VLBW) inants.  There were 274 neonates with gestational ages ranging from 24-32 weeks and birth weights ranging from 401-1500 grams.  The patients receiving ranitidine were similar to the unexposed group in terms of risk factors for infection/NEC, birth weight, gestational age, sex, APGAR scores, PDA, intubation duration, and central vascular access duration.

  • 34 of 91 (37%) exposed to ranitidine developed infections compared with 9.8% of the group not exposed to ranitidine (OR 5.5)
  • Risk of necrotizing enterocolitis (NEC) was 6.6-fold higher among ranitidine-treated neonates
  • Mortality was 9.9% for ranitidine-treated patients compared with 1.6% of control patients
Since gastric acid acts as a defense against ingested pathogens, theoretically inhibition of acid production allows proliferation of these pathogens with subsequent infections and development of necrotizing enterocolitis.  These potential risks and the general lack of benefit of acid suppression in neonates should help guide clinician decision-making.
Another concern with ranitidine has been among acute appendicitis patients (see references below) where it has been associated with an increased likelihood of developing an abscess.

Additional references/previous related blog entries:

Does necrotizing enterocolitis cause neurologic deficits?

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Quite possibly (J Pediatr 2012; 160: 409-14).

There have been recent reports that surgery in preterm and even term infants can affect neurodevelopmental outcomes.  This report, which looked at infants born at <30 weeks or birth weight of <1250 g, adds more information in this area.  The surgery group (n=30) had more white matter injury on MRI and lower developmental scores at 2 years than the nonsurgical group (n=178).  Infants requiring bowel surgery had the worst outcomes.  The exact reasons for these outcomes and the significance are unclear, in part due to the small number of infants with bowel surgery.  Potential factors include inflammatory mediators/cytokines, and anesthesia effects.

The article notes that the FDA has issued warnings regarding anesthetic use in neonates and young children.  These agents may cause abnormalities in the developing brain, particularly in the thalamus.

This study has a number of limitations including the lack of preoperative comparative imaging studies.  Nevertheless, despite unresolved issues regarding causality, it is clear that infants who have necrotizing enterocolitis remain at high risk for poor neurodevelopmental outcomes.

Additional references:

  • -Anesth Analg 2007; 104: 509-20.  Anesthetics in neonates and young children.
  • -J Pediatr 2008; 153: 170-5. Adverse neurodevelopmental outcomes in infants with sepsis or NEC.

Potential and pitfalls of probiotics with necrotizing enterocolitis

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Recent developments in necrotizing enterocolitis (NEC) have focused on the potential role of new biomarkers and preventive strategies (JPEN 2012; 36: 30S-35S).  In this report, the clinical/diagnostic features of NEC are reviewed:

  • classic form develops between 29-32 weeks corrected gestational age
  • features include feeding intolerance, abdominal distention, bloody stools
  • imaging features: pneumotosis intestinalis, portal venous gas, paucity of gas, fixed bowel loops
  • full term or late NEC usually occurs in the setting of risk factors like congenital heart disease, exchange transfusions, gastroschisis, and neural tube defects
  • spontaneous intestinal perforation due to glucocorticoids or indomethacin may be confused with NEC.  It usually occurs earlier than NEC

This review describes the potential for new biomarkers, including urinary I-FABP & fecal calprotectin. These assays would need to be available with very short turn-around time given the often rapid development of NEC.

Finally, this articles discusses the evidence for preventive measures.  Human milk has been shown to decrease NEC and gradual introduction of feedings remains important. With regard to microbial colonization, NEC does not occur until at least 8-10 days postpartum coincident with anerobic bacterial colonization of intestinal tract.

This has led to attempts to alter the colonization to decrease NEC incidence. 16 randomized controlled trials with 14 different probiotics have been completed.  Most are underpowered.  “The available trials do not permit a decision to be made with respect to optimum strain, dosing, or protocol.”  In a cautionary note, a preterm pig model demonstrated an increase NEC incidence with the use of a specific probiotic (Pediatr Res 2011; 69: 10-16).  Furthermore, probiotics are plagued by a lack of adequate quality control.

Additional references:

  • -Ann Surg 2010; 251: 1174-80.  Non-invasive biomarkers for NEC.
  • -J Peds 2011; 158: 672-74.  Caution advised with probiotics for NEC.
  • -J Peds 2011; 159: 392. n=124 cases (248 controls). retrospective study suggested that abx exposure is a risk factor for NEC (3-fold risk).  Abx -marker for illness or true predisposing factor?
  • -NEJM 2011; 364: 255-64.  NEC review.
  • -Cochrane Database Syst Rev 2011; 3: CD005496.  Probiotics for NEC.
  • -NEJM 2011; 364: 1877. Probiotics likely helpful in preemies with birth wt >1000gm.
  • -NEJM 2010; 364: 255.
  • -Pediatrics 2010; 125: 921-30.  Meta-analysis of probiotics for NEC.
  • -JPS 2009; 44: 1072-76. Mortalitiy of NEC expressed by birth weight.
  • –Pediatrics 2008; 122: 693-700. Multicenter trial of probiotics in VLBW for NEC prevention.
  • -J Pediatr 2008; 153: 339. Cluster of NEC due to norovirus.
  • -Pediatrics 2007; 119; e164. Rate of 0.4% among large cohort of infants w/o indocin, steroids & w slow delayed feedings.
  • -Pediatrics 2006; 117: e137. H2-blockers associated with increased NEC (?causal)
  • -Pediatrics 2005; 116: 1064. CRP helpful. If CRP was persistently normal, antibiotics were aborted and enteral feeds restarted safely.
  • -Pediatrics 2005; 115: 1-4 & 171 editorial.  Probiotics decreased NEC in this study.
  • -J Pediatr 2003; 143: 543. Images of pneumotosis.