PEDIATRICS Vol. 109 No. 3 March 2002, pp. 516-517
COMMENTARY |
Studies of Feeding Intolerance in Very Low Birth Weight Infants: Definition and Significance
Abbreviations: VLBW, very low birth weight • NEC, necrotizing enterocolitis • GRV, gastric residual volumes • ICC, interstitial cells of Cajal
How neonatologists feed very low birth weight (VLBW) neonates has traditionally been based on local practices and until recently has not been subjected to rigorous scientific investigation.1 Furthermore, the outcome variables used to assess the efficacy and safety of neonatal feeding practices are often arbitrary and based on local customs. With the prevailing fear of necrotizing enterocolitis (NEC) in most caregivers, feeding strategies are generally based on evidence of intolerance based on increased pregavage residuals or greenish aspirates. Whether this is based on a myth or scientific evidence has not been clearly ascertained. Indeed, there is no uniform definition of "feeding intolerance." As discussed by Mihatsch and colleagues and as evident in the literature, the definition of feeding intolerance varies and is based on an assessment of prefeed gastric residual volumes (GRVs), the color of these GRVs, and associated clinical manifestation such as abdominal distention, emesis, the presence of blood in stool, and apnea with bradycardia.2–5 Even if properly defined, the clinical significance of each of these criteria for feeding intolerance has yet to be determined. Are they predictive of serious disease, such as NEC, a delayed time to achieve full enteric alimentation, or are they developmental physiologic expectations when feeding VLBW neonates?
Pregavage residuals and bilious residuals reflect poor gastric emptying, duodeno-gastric reflux, and gastroduodenal hypomotility. Although gastric emptying may be dependent on infant position, duodenal motility continues to facilitate aboral propagation by virtue of the phase II activity, although coordinated phase III activity (migrating motor complexes) does not appear consistently until 32 weeks’ gestational age.6 Very immature infants have poor gastroduodenal coordination and excessive quiescence in motor activity. It is likely, but not proven in human neonates, that colonic motility also is slow and delayed. The evidences in support of this are: 1) delayed stooling pattern in VLBW neonates, 2) delayed or altered stooling pattern preceding decreased gastroduodenal motility and delayed gastric emptying, and 3) emesis in bowel obstruction or functional ileus is similar to gastric residuals/bilious residuals, as peristalsis is orad.
Studies in young animals suggest that the control systems of gastrointestinal motility are immature at birth because interstitial cells of Cajal (ICC), nerve, and muscle control systems are not fully differentiated. ICC in circular muscle of small intestine and colon were found associated with nerves in lower esophageal sphincter, pylorus, and duodenum, but not in small intestine and colon. Axons in circular muscle were present everywhere usually free of glial covering, indicating ongoing migration or development. No organized deep muscular plexus in small intestine or submuscular plexus in colon was present. Development of nerves and ICC of circular muscle in esophagus and stomach precedes that in the remaining gut.7
Thus, isolated findings related to gastric emptying alone should not be the sole criteria in initiating or advancing feeds. Stooling pattern, abdominal distention, vagal effects from bowel distention, and nature of stools should also be considered.
Mihatsch and coworkers2 have provided neonatologists a service as they attempt to begin to shed light on the significance of GRV and the color of the gastric residuals. Excessive GRV, either determined by percent of the previous feeding or an absolute volume, has been used as a proxy for feeding intolerance and as an early sign of NEC. The current study demonstrated that a GRV of >2 mL for infants <750 g or >3 mL for infants >750 g did not necessarily affect feeding success as determined by the volume of total feeding on day 14. Similarly, the color of the GRV (green, milky, clear) did not predict feeding intolerance. Nonetheless, the volume of feeding on day 14 did correlate with a higher proportion of episodes of zero GRVs and with predominantly milky gastric residuals. Other studies have suggested that feeding intolerance is also correlated with lower birth weight, birth weight <1000 g, a delay to full enteral feedings, and a delay in achieving discharge weight.5 In addition, improvements in feeding tolerance have been consistently reported with trophic feedings (gut-priming, minimal caloric feedings).8,9
The study by Mihatsch et al 2 is valuable in that it raises more questions that need to be answered in a scientific manner. These important questions include: What is the absolute volume or percentage of a prior feeding that represents feeding intolerance or an early sign of NEC? Studies have not consistently demonstrated a large increase in GRV preceding the onset of NEC.2,4 Is there a threshold effect or is there a gradient that increases risks as the GRV increases? What is the proper response to an "at-risk" GRV? Is it nothing by mouth and for how long? Is it to refeed the GRV, discard it, or to reduce the volume of the subsequent enteral feedings?
The results of Mihatsch’s study2 must not be generalized because they may not be appropriate for infants fed at incremental rates greater than 12 mL/kg/d or with a different formula. Furthermore, the significance of the GRV must always be correlated with the presence of abdominal distention or tenderness, emesis, bloody stools, or apnea and bradycardia. To date, we have yet to define the "at-risk" GRV or the appropriate therapeutic response once it is identified. We look forward to more scientifically-based investigations to help provide recommendations for safe, effective feeding protocols for VLBW neonates.
Department of Pediatrics
Medical College of Wisconsin
Milwaukee, WI 53226
FOOTNOTES
Received for publication Nov 9, 2001; Accepted Nov 9, 2001.
Address correspondence to Robert M. Kliegman, MD, Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226.
REFERENCES
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3. Dollberg S, Kuint J, Mazkereth R, et al. Feeding tolerance in preterm infants: randomized trial of bolus and continuous feeding. J Am Coll Nutr.2000; 19 :797 –800[Medline]
4. Rayyis SF, Ambalavanan N, Wright L, et al. Randomized trial of "slow" versus "fast" feed advancements on the incidence of necrotizing entercolitis in very low birth weight infants. J Pediatr.1999; 134 :293 –297[Medline]
5. Akintorin SM, Kamat M, Pildes RS, et al. A prospective randomized trial of feeding methods in very low birth weight infants. Pediatrics.1997; 100(4) . Available at: http://www.pediatrics.org/cgi/content/full/100/4/e4
6. Jadcherla SR, Klee G, Berseth CL. Regulation of migrating motor complexes by motilin and pancreatic polypeptide in human infants. Pediatr Res.1997; 42 :365 –369[Abstract]
7. Daniel EE, Wang YF. Control systems of gastrointestinal motility are immature at birth in dogs. Neurogastroenterol Motil.1999; 11 :375 –392[Medline]
8. Slagle TA, Gross SJ. Effect of early low-volume enteral substrate on subsequent feeding tolerance in very low birth weight infants. J Pediatr.1988; 113 :526 –531[Medline]
9. Dunn L, Hulman S, Weiner J, et al. Beneficial effects of early hypocaloric enteral feeding on neonatal gastrointestinal function: preliminary report of a randomized trial. J Pediatr.1988; 112 :622 –629[Medline]
PEDIATRICS (ISSN 1098-4275). ©2002 by the American Academy of Pediatrics
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