PEDIATRICS Vol. 109 No. 3 March 2002, pp. 423-428
Impact of Necrotizing Enterocolitis on Length of Stay and Hospital Charges in Very Low Birth Weight Infants
Department of Pediatrics, Section of Neonatology, Baylor College of Medicine, Houston, Texas
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONPARTICIPANTS AND METHODSData AnalysisRESULTSDISCUSSIONREFERENCES |
|---|
Objective. To determine the impact of necrotizing enterocolitis (NEC) on length of stay and hospital charges.
Design. Case-control study.
Setting. Two neonatal intensive care units in an academic medical center.
Patients. Infants born in 1992–1994 with birth weight <1500 g, matched by gestational age, hospital, and month of birth.
Measurements and Main Results. We performed odds ratio and t testing. As with previous studies, there was no single factor that increased the risk for developing NEC. However, the diagnosis of NEC increased the risk for death, infection, and the need for central line placement. Infants with surgical NEC had lengths of stay that exceeded those of controls by 60 days, whereas lengths of stay among infants with medical NEC exceeded those of controls by 22 days. Based on length of stay, the estimated total hospital charges for infants with surgical NEC averaged $186 200 in excess of those for controls and $73 700 more for infants with medical NEC. The yearly additional hospital charges for NEC were $6.5 million or $216 666 per survivor.
Conclusions. A diagnosis of NEC in the very low birth weight infant imposes a significant additional financial burden to the individual patient as well as the neonatal community as a whole. This expense justifies additional research into preventive measures and potentially costly therapies aimed at reducing the incidence of NEC. These data also provide an estimated cost to compare the cost effectiveness of new preventive measures for NEC.
Key Words: necrotizing enterocolitis • very low birth weight infants • length of stay • hospital charges
Abbreviations: NEC, necrotizing enterocolitis • SGA, small for gestational age • PDA, patent ductus arteriosus • UAC, umbilical arterial catheter • UVC, umbilical venous catheter • ROP, retinopathy of prematurity • BPD, bronchopulmonary dysplasia • LOS, length of stay • NICU, neonatal intensive care unit • OR, odds ratio • CI, confidence interval
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONPARTICIPANTS AND METHODSData AnalysisRESULTSDISCUSSIONREFERENCES |
|---|
Approximately 5% to 10% of very low birth weight infants develop necrotizing enterocolitis (NEC).1–4 Although previous studies have investigated the relationship of NEC with a variety of predisposing risk factors including lack of exposure to antenatal steroids, black race, birth weight that is small for gestational age (SGA), diagnosis of patent ductus arteriosus (PDA), placement of an umbilical arterial catheter (UAC), and placement of an umbilical venous catheter (UVC),5–9 there is no consistent agreement that these are independent risk factors.4,10,11 All of these previous studies have attempted to identify risk factors or events that precede a diagnosis of NEC. Several studies have described the long-term outcome of NEC with respect to the need for surgery,12,13 death,13,14 the development of short gut,13,15 and the occurrence of adhesions.15,16 However, the impact of NEC on other risk factors or events that occur after the diagnosis of NEC has not been assessed.
During their initial acute illness, infants with NEC often require ventilator and oxygen support.17–19 It has been our empiric observation that infants who require surgery for NEC develop more morbidity, such as infection, retinopathy of prematurity (ROP), or bronchopulmonary dysplasia (BPD), which lengthen hospital stay.20–22 We designed our study to test the hypothesis that having a diagnosis of NEC increases risk for other morbidity and increases the length of stay (LOS).
|
PARTICIPANTS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONPARTICIPANTS AND METHODSData AnalysisRESULTSDISCUSSIONREFERENCES |
|---|
We identified all infants whose birth weights were <1500 g and were admitted to the neonatal intensive care units (NICUs) at Texas Children’s Hospital and Ben Taub General Hospital from January 1992 to December 1994, who developed NEC, defined as Bell’s stage II or greater.23 A dedicated registered nurse prospectively collected all data concerning these infants into a database in a contemporaneous uniform manner, as we have previously reported.24 We performed a case-control analysis.
We identified infants with surgical NEC and medical NEC by chart review. We defined surgical NEC to occur in 2 groups of infants. The first group consisted of those who developed radiographic evidence of perforated bowel, and the second group was composed of infants who did not have radiographic evidence of perforated bowel but who underwent exploratory laparatomy during the first week after diagnosis because of severe clinical deterioration despite aggressive medical therapy. We excluded from the study 5 infants who had spontaneous ileal perforations. Infants who required surgery for strictures several weeks after the diagnosis of medical NEC were considered to have medical NEC. We matched each case of surgical NEC and medical NEC to 2 controls by hospital of birth, gestational age, and month of birth. Care was taken to select control infants who survived at least until their matched cases developed NEC. We abstracted information concerning gender, ethnicity, exposure to antenatal steroids, presence of PDA, SGA status, UAC or UVC placement, and day of onset of NEC. We also recorded the following outcomes: death during the initial neonatal hospitalization, infection, ROP, BPD, intraventricular hemorrhage, and central line placement. We defined infection as the occurrence of any positive blood culture, BPD as the need for oxygen beyond 28 days, and central line placement as any percutaneously or surgically placed venous catheter (excluding UVCs). For infants with surgical NEC, we recorded the time interval between the initial diagnosis of NEC and the presence of free air if serial radiograph evaluations were done. We noted the LOS in level III and level II nurseries and overall LOS in the hospital for the initial neonatal hospitalization of infants who survived to discharge and those who died.
The routine care of infants with NEC during this time period was fairly uniform. When the diagnosis of NEC was suspected, feedings were stopped, blood samples for cultures were obtained, antibiotics were begun, and parenteral nutrition resumed. Serial abdominal radiographs were performed to detect whether free air was present in the abdomen. The usual indication for surgery was the presence of free air in the abdomen or deterioration in clinical stability despite aggressive medical management. Surgery consisted of exploratory laparotomy, including bowel resection if indicated. Peritoneal drains were placed in lieu of laparotomy in 1 patient. Central lines were placed in infants with medical NEC 3 days after diagnosis if blood cultures were negative. These infants were refed 10 to 14 days later. Central lines were placed in infants with surgical NEC 2 days postoperatively, although a few were placed at the time of the initial laparotomy. Infants with surgical NEC were refed in consultation with the surgical team.
Infants were admitted to the level III nursery if they required ventilator support or nasal continuous positive airway pressure. Those who did not require this type of respiratory support were generally transferred to the level II nursery. The majority of infants were discharged from the hospital when they were breathing spontaneously without supplemental oxygen, taking all feeds by mouth and gaining weight adequately. A few infants were discharged with supplemental oxygen and gavage feedings.
|
Data Analysis |
|---|
|
TOPABSTRACTINTRODUCTIONPARTICIPANTS AND METHODSData AnalysisRESULTSDISCUSSIONREFERENCES |
|---|
We calculated odds ratios (ORs) with 95% confidence intervals (CIs) to identify risks for morbidity. We estimated the total hospital charges based on the LOS in level III and level II using hospital charges reported from the same institutions during the same time period.25 In short, for each infant we multiplied the LOS in level II times the mean daily hospital charges for level II care,25 multiplied the LOS in level III times the mean daily hospital charges for level III care25 and summed the products. We performed
2 analysis and used Fisher exact testing and Student t testing where appropriate. All normally distributed data were expressed as mean ± standard deviation. |
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONPARTICIPANTS AND METHODSData AnalysisRESULTSDISCUSSIONREFERENCES |
|---|
Eight hundred sixty-six infants with birth weight <1500 g were admitted to the neonatal intensive care unit during the 2-year study period. Eighty-six (10%) of these developed NEC. Of the 86 infants who met the inclusion criteria, 60 were admitted to Texas Children’s Hospital and 26 to Ben Taub General Hospital; 49 (57%) were defined to have medical NEC and 37 (43%) surgical NEC. All 86 cases were successfully matched with 2 controls. Characteristics of medical NEC and surgical NEC cases and their respective controls are shown in Table 1. Infants with medical and surgical NEC had similar birth weights (Table 1; P = .13) and gestational ages (Table 1; P = .3). We assessed the presence of risk factors for NEC among medical NEC and surgical NEC cases. As shown in Table 2, male gender, race, lack of exposure to antenatal steroids, a diagnosis of PDA, and placement of UVC or UAC were not associated with an increased risk of developing either medical or surgical NEC.
|
|
Of the 37 infants who had surgical NEC, 27 had radiographic evidence of perforated bowel and 8 had clinical deterioration despite aggressive medical management. Of these 8 latter infants, 4 were found to have bowel perforation at the time of surgery. Radiographs could not be located for 2 infants. Of those who required surgery for the radiographic evidence of bowel perforation, 85% were diagnosed within 72 hours of their initial diagnosis (Fig 1).
|
The diagnosis of medical NEC increased the risk for death by 13.9-fold (Table 3; P < .001), the need for central line placement by 4.7-fold (Table 3; P = .004), and the risk for infection by fourfold (Table 3; P < 001), but it did not increase the risk for BPD or ROP. In a similar fashion, the diagnosis of surgical NEC increased the risk for death by 24.5, the need for central line placement by 14, and the risk for infection by 5.7 (Table 3; all P < .001), whereas the risks for BPD or ROP were similar between cases and controls.
|
Survivors of medical NEC stayed in Level III nursery 54 ± 33 days compared with 38 ± 22 days for controls (Table 4; P < .001). Although the LOS in Level II days was similar between cases and controls, overall LOS was 95 ± 42 days for survivors of medical NEC compared with 73 ± 27 days for their controls (Table 4; P < .001). As a result, overall hospital charges for survivors of medical NEC were $303 779 ± $137 157 compared with $230 099 ± $88 070 for control infants (Table 4; P = .009). In contrast, survivors of surgical NEC stayed in Level III nursery 73 ± 60 days compared with 48 ± 25 days for controls (Table 4; P = 0.004); they stayed in Level II nursery 68 ± 46 days compared with 34 ± 20 days for controls (Table 4; P < .001); and their overall LOS was 142 ± 65 days compared with 82 ± 31 days for controls (Table 4; P < .001). Overall hospital charges for survivors of surgical NEC were $448 000 ± $210 229 compared with $261 800 ± $99 844 for controls (Table 4; P < .001). Because of their prolonged hospital stays, infants with surgical NEC weighed significantly more than controls at the time of discharge (Table 1; P < .001).
|
Nonsurvivors of medical NEC had an overall LOS of 60 ± 45 days compared with 65 ± 21 days among controls who did not survive, and their total hospital charges were $204 272 ± $153 858 compared with $243 100 ± $69 721 for controls (Both nonsignificant). Nonsurvivors of surgical NEC had overall LOS of 48 ± 30 days compared with 37 ± 19 days for controls, and they had hospital charges of $161 493 ± $99 092 compared with $107 100 ± $64 912 for controls (Both nonsignificant). Although mortality was higher in infants with surgical NEC, about half died during the first week after the diagnosis and another half died during the second week. As a result, survival after the third week after diagnosis was similar among infants with medical NEC and surgical NEC (Fig 2).
|
Twenty-six (30%) of 86 of infants with NEC died. Based on data from control infants shown in Table 1, we would have anticipated that only 3% would have died. Therefore, we considered 97% of costs incurred by NEC nonsurvivors to be "lost" to NEC. For infants who survived, we considered the charges "lost" to NEC to be the difference between the overall charges between the cases and controls. Thus, the additional charges incurred for treating infants with NEC was $6.7 million for medical NEC and $6.3 million for surgical NEC, resulting in an overall additional expense of $13 million for the NICUs at Baylor College of Medicine during the 2-year study period. The total additional yearly hospital charges for NEC were $6.5 million and $216 666 per survivor.
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONPARTICIPANTS AND METHODSData AnalysisRESULTSDISCUSSIONREFERENCES |
|---|
Our study demonstrates that a diagnosis of NEC among very low birth weight infants is very costly for the individual patient as well as the neonatal community. Based on our data, we can counsel the parents of a infant who develops NEC in our NICU that their infant has a 70% chance of survival. If surgical NEC is not initially present, the highest risk for bowel perforation is during the first 72 hours after diagnosis. Mortality among infants who develop surgical NEC is highest during the first 2 weeks of the disease. If the infant with surgical NEC survives 3 weeks after the diagnosis, survival rates are similar to those for infants with medical NEC. If the infant has medical NEC and survives, he will stay in the hospital for an additional 22 days and incur additional hospital charges of $73 700. If he develops surgical NEC and survives to be discharged from his initial neonatal hospitalization, he will stay in the hospital for an additional 2 months and incur additional hospital charges of $186 200.
As a result of the additional hospital charges for infants with NEC, our neonatal community spent an additional $6.5 million annually treating infants with NEC, or $216 666 per survivor, during 1992–1994. Adjusting for inflation, we estimate that the total additional hospital charges in our institution attributable to NEC alone are $7.2 million per year and $238 333 per survivor. It is important to realize that these numbers reflect hospital charges only, and thus, are conservative estimates of the true cost of this disease, as they do not include physician charges. This estimate also does not take into account the cost of "NEC scares" when infants are given parenteral nutrition and antibiotics for several days. It should also be noted that this analysis was limited to infants whose birth weights were <1500 g, and data may not reflect the experience of those infants whose birth weights exceed 1500 g.
Approximately 300 000 infants with birth weights <1500 g were born in the United States in 1998.26 If we estimate the incidence of NEC to be 10% and the incidence of mortality of NEC to be 30%, we estimate that $5 billion is spent annually by the neonatal community on NEC. This additional cost constitutes approximately 19% of the total costs of initial care for all newborns in the United States.27 Thus, NEC is a significant public health issue for the neonatal community and our data confirm the need for more research dollars for prevention and better treatment of this disease.
Several strategies for the prevention of NEC have been proposed including delaying of the initiation of feeding,28,29 minimal enteral feeding regimens,29,30 dietary supplements including egg phospholipid,31 lactobacillus,32,33 oligofructose,34 and the administration of immunoglobulin G-immunoglobulin A.35 Although these strategies may reduce the incidence of NEC, they do so at the expense of increasing LOS36 and incurring costs for administering preventive dietary supplements unnecessarily to infants who do not go on to develop NEC. Our data will permit the cost of these preventive strategies to be weighed against the cost of treating NEC.
Previous investigators have suggested that NEC represents neonatal multisystem organ failure,37,38 a well-recognized syndrome in adults of sequential deterioration of respiratory, hepatic, renal, hematologic, and cardiac function, in which breakdown of gastrointestinal mucosal barriers plays an important role. Although infants with NEC had a higher incidence of sepsis, they had no other evidence of multisystem morbidity, as reflected by BPD or intraventricular hemorrhage. Although LOS may be increased among infants with late sepsis,20,47 the longer LOS of infants with NEC could not be attributed to BPD. Because cases were matched with controls by gestational age, the influence of prematurity on the LOS was controlled in our study. Nor does it appear that the LOS among infants with surgical NEC was attributable to younger gestational age, as the gestational ages among infants with medical NEC and surgical NEC were similar. We speculate that infants with surgical NEC were sicker and less clinically stable than infants who developed medical NEC. However, our study design did not permit us to test this hypothesis. An alternative explanation is that surgery itself causes trauma and stress. If this is the case, the increasing use of peritoneal drains in lieu of laparotomy may permit the testing of this second hypothesis in the near future.39–41
The mortality rate for infants with surgical NEC was similar to that reported by others.42,43 The high risk for infection may reflect that 26% to 40% of NEC cases are subsequently found to have positive blood cultures at the time of diagnosis.44,45 We speculate that the remaining episodes were attributable to central line infections.46 Stoll and associates22 have reported that infants with late onset infections are more likely to develop BPD and NEC, whereas Leroyer and associates47 have noted that neonates who develop hospital-acquired infections experience longer LOSs and extra hospital costs. Ehrenkranz and associates48 have noted that infants in National Institute of Child Health and Human Development nurseries with chronic morbidity, such as BPD, severe intraventricular hemorrhage, NEC, and late onset sepsis had slower weight gain than those who did not have these entities. Although one could speculate that hospitalizations were prolonged among infants with surgical NEC because of poor weight gain secondary to increased metabolic needs imposed by NEC, BPD, or infection, their discharge weights were significantly greater than their controls. When one calculates that additional number of hospital days that surgical NEC infants experienced, we estimate that these infants gained approximately 18 g/day. Thus, we conclude that poor weight gain was not a contributing factor to their prolonged hospital stays.
|
FOOTNOTES |
|---|
Received for publication Mar 27, 2001; Accepted Aug 16, 2001.
Reprint requests to (C.L.B.) Department of Pediatrics, Section of Neonatology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. E-mail: cberseth{at}neo.bcm.tmc.edu
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONPARTICIPANTS AND METHODSData AnalysisRESULTSDISCUSSIONREFERENCES |
|---|
1. Uauy RD, Fanaroff AA, Korones SB, et al. Necrotizing enterocolitis in very low birth weight infants: biodemographics and clinical correlates. J Pediatr.1991; 119 :630 –638[Medline]
2. The Investigators of the Vermont-Oxford Trials Network Database Project. The Vermont-Oxford Trials Network. Very low birth weight outcomes for 1990. Pediatrics.1993; 91 :540 –545[Abstract]
3. Fanaroff AA, Wright LL, Stevenson DK, Shankaran S, Donovan EF, Ehrenkranz RA. Very-low-birth weight outcomes of the National Institutes of Child Health and Human Development Neonatal Research Network, May 1991 through December 1992. Am J Obstet Gynecol.1995; 173 :1423 –1431[Medline]
4. Stoll BJ, Kanto WP Jr, Glass RI, Nahmias AJ, Brann AW. Epidemiology of necrotizing enterocolitis: a case control study. J Pediatr.1980; 96 :447 –451[Medline]
5. Wiswell TE, Robertson CF, Jones TA, Tuttle DJ. Necrotizing enterocolitis in full-term infants: a case control study. Am J Dis Child.1988; 142 :532 –535[Medline]
6. Livaditis A, Walgren G, Faxelius G. Necrotizing enterocolitis after catheterization of umbilical vessels. Acta Paediatr Scand.1974; 63 :277 –282[Medline]
7. Holman RC, Stoll BJ, Clarke MJ, Glass RI. The epidemiology of necrotizing enterocolitis infant mortality in the United States. Am J Public Health.1997; 87 :2026 –2031[Abstract]
8. Palder SB, Schwartz MZ, Tyson KR, Marr CC. Association of patent ductus arteriosus and development of necrotizing enterocolitis. J Pediatr Surg.1988; 23 :422 –423[Medline]
9. Mizrahi A, Barlow O, Berdon W, Blanc W, Silverman W. Necrotizing enterocolitis in premature infants. J Pediatr.1965; 66 :697 –706
10. Kliegman RM, Hack M, Jones P, Fanaroff AA. Epidemiologic study of necrotizing enterocolitis among low-birth-weight infants: absence of identifiable risk factors. J Pediatr.1982; 100 :440 –444[Medline]
11. Yu VYH, Joseph R, Bajuc B, Orgill A, Astbury J. Perinatal risk factors of necrotizing enterocolitis. Arch Dis Child.1984; 59 :430 –434[Abstract]
12. Grosfeld JL, Cheu H, Schlatter M, West KW, Rescorla FJ. Changing trends in necrotizing enterocolitis. Experience with 302 cases in two decades. Ann Surg.1991; 214 :300 –306[Medline]
13. Ricketts RR. Surgical therapy for necrotizing enterocolitis. Ann Surg.1984; 200; 653 –657[Medline]
14. Ladd AP, Rescorla FJ, West KW, Scherer LR III, Engum SA, Grosfeld JR. Long-term follow-up after bowel resection for necrotizing enterocolitis: factors affecting outcome. J Pediatr Surg.1998; 33 :967 –972[Medline]
15. Jackman S, Brereton RJ, Wright VM. Results of surgical treatment of neonatal necrotizing enterocolitis. Br J Surg.1990; 77 :146 –148[Medline]
16. Pokorny WJ, Garcia-Prats JA, Barry YN. Necrotizing enterocolitis: incidence, operative care, and outcome. J Pediatr Surg.1986; 21 :1149 –1154[Medline]
17. Kanto WP Jr, Wilson R, Ricketts RR. Management and outcome of necrotizing enterocolitis. Clin Pediatr.1985; 24 :79 –82
18. Kanto WP Jr, Hunter JE, Stoll JB. Recognition and medical management of necrotizing enterocolitis. Clin Perinatol.1994; 21 :335 –346[Medline]
19. O’Neill JA. Neonatal necrotizing enterocolitis. Surg Clin North Am.1981; 61 :1013 –1022[Medline]
20. Bannwart D de C, Rebello CM, Sadeck LS, Pontes MD, Ramos JL, Leone CR. Prediction of length of hospital stay in neonatal units for very low birth weight infants. J Pedinatol.1999; 19 :92 –96
21. Yeo CL, Choo S, Ho LY. Chronic lung disease in very low birth weight infants: a 5-year review. J Paediatr Child Health.1997; 33 :102 –106[Medline]
22. Stoll BJ, Gordon T, Korones SB, et al. Late-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network. J Pediatr.1996; 129 :63 –71[Medline]
23. Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L. Neonatal necrotizing enterocolitis, therapeutic decision based upon clinical staging. Ann Surg.1978; 187 :1 –7[Medline]
24. Cooper TR, Berseth CL, Adams JM, Weisman LE. Actuarial survival in the premature infant less than 30 weeks. Pediatrics.1998; 101 :975 –978[Abstract/Full Text]
25. Adams JM, Moreno J, Reynolds K, et al. Resource utilization among neonatologists in a university children’s hospital. Pediatrics.1997; 99(6) . Available at: http://www.pediatrics.org/cgi/content/full/99/6/e2
26. Guyer B, Hoyert DL, Martin JA, Ventrua SJ, MacDorman MF, Strobino DM. Annual summary of vital statistics—1998. Pediatrics.1999; 104 :1229 –1246[Abstract/Full Text]
27. St John EB, Nelson KG, Cliver SP, Bishnoi RR, Goldenberg RL. Cost of neonatal care according to gestational age at birth and survival status. Am J Obstet Gynecol.2000; 182 :170 –175[Medline]
28. Brown EG, Sweet AY. Preventing necrotizing enterocolitis in neonates. JAMA.1978; 240 :2452 –2454[Medline]
29. McKeown RE, Marsh TD, Amarnath U, Garrison CZ, Addy CL, Thompson SJ. Role of delayed feeding and feeding increments in necrotizing enterocolitis. J Pediatr.1992; 121 :764 –770[Medline]
30. Lucas A, Bloom SR, Aynsley-Green A. Gut hormones and "minimal enteral feeding." Acta Paediatr Scand.1986; 75 :719 –723[Medline]
31. Carlson SE, Montalto MB, Ponderb DL, Werkman SH, Korones SB. Lower incidence of necrotizing enterocolitis in infants fed a preterm formula with egg phospholipids. Pediatr Res.1998; 44 :491 –498[Abstract]
32. Caplan MS, Miller-Catchpole R, Kaup S, Russe T, Lickerman M, Am M. Bifidobacterial supplementation reduces the incidence of necrotizing enterocolitis in a neonatal rat model. Gastroenterology.1999; 117 :577 –583[Abstract/Full Text]
33. Hoyos AB. Reduced incidence of necrotizing enterocolitis associated with enteral administration of Lactobacillus acidophilus and Bifidobacterium infantis to neonates in an intensive care unit. Int J Infect Dis.1999; 3 :197 –202[Medline]
34. Catala I, Butel MJ, Bensaada M, Popot F, Tessedre AC, Rimbault A. Oligofructose contributes to the protective role of bifidobacteria in experimental necrotising enterocolitis in quails. J Med Microbiol.1999; 48 :89 –94[Medline]
35. Eibl MM, Wolf HM, Furkranz H, Rosenkranz A. Prevention of necrotizing enterocolitis in low birth weight infants by IG A-IgG feeding. N Engl J Med.1988; 319 :1 –7[Abstract]
36. Rayyis SF, Ambalavanan N, Wright L, Carlo WA. Randomized trial of "slow" versus "fast" feed advancements on the incidence of necrotizing enterocolitis in very low birth weight infants. J Pediatr.1999; 134 :293 –297[Medline]
37. Morecroft JA, Spitz L, Hamilton PA, Holrmes SJ. Necrotizing enterocolitis—multisystem organ failure of the newborn? Acta Paediatr Suppl.1994; 396 :21 –23[Medline]
38. Smith SD, Tagge EP, Hannakan C, Rowe MI. Characterization of neonatal multisystem organ failure in the surgical newborn. J Pediatr Surg.1991; 26 :494 –499[Medline]
39. Ahmed T, Ein S, Moore A. The role of peritoneal drains in treatment of perforated necrotizing enterocolitis: recommendations from recent experience. J Pediatr Surg.1998; 33 :1468 –1470[Medline]
40. Rovin JD, Rodgers BM, Burns RC, McGharen ED. The role of peritoneal drainage for intestinal perforation in infants with and without necrotizing enterocolitis. J Pediatr Surg.1999; 34 :143 –147[Medline]
41. Azarow KS, Ein SH, Shandling B, Wesson D, Superina R, Filler RM. Laparotomy or drain for perforated necrotizing enterocolitis: who gets what and why? Pediatr Surg Int.1997; 12 :137 –139
42. Ladd AP, Rescorla FJ, West KW, Scherer LR III, Engum SA, Grofeld JL. Long-term follow-up after bowel resection for necrotizing enterocolitis: factors affecting outcome. J Pediatr Surg.1998; 33 :967 –972[Medline]
43. Lemelle JL, Schmitt M, de Miscault G, et al. Neonatal necrotizing enterocolitis: a retrospective and muticentric review of 331 cases. Acta Paediatr Suppl.1994; 396 :70 –73[Medline]
44. Owens L, Berseth CL. Clinical presentation of necrotizing enterocolitis (NEC) differs between very low birth weight (VLBW) and low birth weight (LBW) infants. J Clin Invest Med.1996; 44 :14A
45. Chan KL, Saing H, Yung RWH, Yeung UP, Tsoi NS. A study of pre-antibiotic bacteriology in 125 patients with necrotizing enterocolitis. Acta Paediatr Suppl.1994; 396 :45 –48[Medline]
46. Brodie SB, Sands KE, Gray JE, et al. Occurrence of nosocomial bloodstream infections in six neonatal intensive care units. Pediatr Infect Dis J.2000; 19 :56 –65[Medline]
47. Leroyer A, Bedy A, Lombrail P, Desplanques L, Diakite B, Bingen E. Prolongation of hospital stay and extra costs due to hospitalization acquired infection in a neonatal unit. J Hosp Inf.1997; 35 :37 –45
48. Ehrenkranz RA, Younes N, Lemons JA, Fanaroff AA, Donovan EF, Wright LL. Longitudinal growth of hospitalized very low birth weight infants. Pediatrics.1999; 104 :280 –289[Abstract/Full Text]
PEDIATRICS (ISSN 1098-4275). ©2002 by the American Academy of Pediatrics
CiteULike 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  F. Abdullah, Y. Zhang, M. Camp, D. Mukherjee, A. Gabre-Kidan, P. M. Colombani, and D. C. Chang Necrotizing Enterocolitis in 20 822 Infants: Analysis of Medical and Surgical Treatments Clinical Pediatrics, March 1, 2010; 49(2): 166 - 171. [Abstract] [PDF]
|
|
|
|
 |
|
 T. Anderson, A. Lord, N. Shotkoski, and C. O'Keefe The Use of Probiotics for the Prevention of Necrotizing Enterocolitis in the Premature Infant ICAN: Infant, Child, & Adolescent Nutrition, October 1, 2009; 1(5): 246 - 252. [Abstract] [PDF]
|
|
|
|
 |
|
 C. R. Cole, N. I. Hansen, R. D. Higgins, T. R. Ziegler, B. J. Stoll, and for the Eunice Kennedy Shriver NICHD Neonatal Rese Very Low Birth Weight Preterm Infants With Surgical Short Bowel Syndrome: Incidence, Morbidity and Mortality, and Growth Outcomes at 18 to 22 Months Pediatrics, September 1, 2008; 122(3): e573 - e582. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Wang, C. Anderson, T. A. Leone, W. Rich, B. Govindaswami, and N. N. Finer Resuscitation of Preterm Neonates by Using Room Air or 100% Oxygen Pediatrics, June 1, 2008; 121(6): 1083 - 1089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Sisk, C. A. Lovelady, K. J. Gruber, R. G. Dillard, and T. M. O'Shea Human Milk Consumption and Full Enteral Feeding Among Infants Who Weigh <=1250 Grams Pediatrics, June 1, 2008; 121(6): e1528 - e1533. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F Williams, C. C Kingdon, and G. Weaver Banking for the future: investing in human milk Arch. Dis. Child. Fetal Neonatal Ed., May 1, 2007; 92(3): F158 - F159. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Updegrove Necrotizing Enterocolitis: the Evidence for Use of Human Milk in Prevention and Treatment J Hum Lact, August 1, 2004; 20(3): 335 - 339. [Abstract] [PDF]
|
|
|
|
|
|
C. L. Berseth, J. A. Bisquera, and V. U. Paje Prolonging Small Feeding Volumes Early in Life Decreases the Incidence of Necrotizing Enterocolitis in Very Low Birth Weight Infants Pediatrics, March 1, 2003; 111(3): 529 - 534. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
