Safety of Enteral Feed Volumes in Neonates at Risk for Necrotizing Enterocolitis: The Never-Ending Story
Sanjay Patole, MD, DCH, FRACPDepartment of Neonatal Paediatrics
King Edward Memorial Hospital for Women
Perth 6008, Western Australia
To the Editor. —
We read with interest the recent article by Berseth et al1 and wish to report the following observations.
First, the rationale behind desiring a –67% reduction (from 12% to 4%) in the incidence of necrotizing enterocolitis (NEC) is not very clear. This must be one of the uncommon occasions on which a clinical trial has successfully detected such a large desired treatment effect.2 The authors state that the sample size has been estimated to detect (with 80% power) such a reduction based on the low incidence "in studies that compared minimal enteral feedings to no feedings," and the higher incidence "in a study that used larger feeding volumes."1 Of the 2 studies in relation to low incidence of NEC and minimal enteral feeds (both using hypocaloric feeds and conducted years ago), the one by Berseth et al3 does not provide any data on the occurrence of NEC. The other study by Dunn et al4 reported that the incidence of NEC "did not differ between the NPO and the PO group (5% vs 16%[?]), although the number of patients is too small to avoid a type II error" (italics were added for emphasis). The reference5 quoted for the statement in relation to "larger feeding volumes and NEC" covers 5 studies (audit,6 case-control studies,7–9 and a prospective controlled trial with no clear of specification about randomization10) conducted on patients born between 1964 and 1990. Institutional and relatively recent data would have been more appropriate for planning such an important study to cover for changes in clinical practice over years and increasing survival of neonates <1000 g at birth, who are at the highest risk for NEC.
Second, the baseline incidence of NEC was significant (12%), whereas the frequency of antenatal steroids (study: 51%; control: 63%) and breast milk usage (study: 34%; control: 25%), factors known to be protective toward development of NEC, was low. It is therefore not surprising that, of the entire "higher-risk" population, the neonates allocated to the "advancing feeds" group (20 mL/kg per day increments, considered "safe") had an alarmingly high incidence of NEC, compared with the control group. The occurrence of NEC in such a high number of neonates despite having an algorithm11 based only on gastric residual volume also indicates the unreliability of clinical signs in the early detection of NEC.
Third, Berseth et al comment that "larger feeding volumes increased the risk for NEC in the current study, but that increase in risk was not offset by an increase in benefit."1 One wonders what benefits would be worth the development of a potentially devastating illness such as NEC in a significant number of neonates as in this study.
Last, it would have been helpful to know the incidence of intrauterine growth restriction in both the study groups.
In summary, the results of this study simply confirm that a "universally safe" enteral feed volume (daily total or increments per kg) for high-risk neonates can never be defined. Given the difficulties in interpretation of signs of "feed intolerance" ("ileus of prematurity") and the current philosophy of aggressive enteral nutrition of high-risk neonates, an iatrogenic surge in the incidence of NEC will be inevitable as long as we continue to expect numbers (mL/kg of enteral feeds) to provide safety.
REFERENCES
- Berseth CL, Bisquera JA, Paje VU. Prolonging small feeding volumes early in life decreases the incidence of necrotizing enterocolitis in very low birth weight infants.
Pediatrics. 2003;111
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[Abstract/Free Full Text] - Zhang B, Schmidt B. Do we measure the right end points? A systematic review of primary outcomes in recent neonatal randomized clinical trials. J Pediatr. 2001;138 :76 –80[CrossRef][Web of Science][Medline]
- Berseth CL. Effect of early feeding on maturation of the preterm infant’s small intestine. J Pediatr. 1992;120 :947 –953[CrossRef][Web of Science][Medline]
- Dunn L, Hulman S, Weiner J, Kliegman R. Beneficial effects of early hypocaloric enteral feeding on neonatal gastrointestinal function: preliminary report of a randomized trial. J Pediatr. 1988;112 :622 –629[CrossRef][Web of Science][Medline]
- La Gamma EF, Browne LE. Feeding practices for infants weighing less than 1500 G at birth and the pathogenesis of necrotizing enterocolitis. Clin Perinatol. 1994;21 :271 –306[Web of Science][Medline]
- Goldman HI. Feeding and necrotizing enterocolitis.
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[Abstract/Free Full Text] - Covert RF, Neu J, Elliott MJ, Rea JL, Gimotty PA. Factors associated with age of onset of necrotizing enterocolitis. Am J Perinatol. 1989;6 :455 –460[Medline]
- Anderson DM, Kliegman RM. The relationship of neonatal alimentation practices to the occurrence of endemic necrotizing enterocolitis. Am J Perinatol. 1991;8 :62 –67[Web of Science][Medline]
- McKeown RE, Marsh TD, Amarnath U, et al. Role of delayed feeding and of feeding increments in necrotizing enterocolitis. J Pediatr. 1992;121 :764 –770[CrossRef][Web of Science][Medline]
- Book LS, Herbst JJ, Jung AL. Comparison of fast- and slow-feeding rate schedules to the development of necrotizing enterocolitis. J Pediatr. 1976;89 :463 –466[CrossRef][Web of Science][Medline]
- Schanler RJ. The low-birth-weight infant. In: Walker WA, Watkins JB, eds. Nutrition in Pediatrics: Basic Science and Clinical Application. 2nd ed. Hamilton, ON, Canada: BC Decker; 1996:392 –412
PEDIATRICS (ISSN 1098-4275). ©2004 by the American Academy of Pediatrics
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