Necrotising Enterocolitis(NEC) - Clinical features, investigations and management. Bells staging complications of NEC

1. Necrotising Enterocolitis
Sid Kaithakkoden MD
alavisaid@aol.com

2. Index
• Case presentation
• Aetiology
• Path physiology
• Clinical findings
• Differential diagnosis
• Investigations
• Management
• Prognosis & complications
• Recent advances & Cochrane reviews
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3. Case Presentation
• Baby P, born at 36 weeks, SVD
• Apgar 9/1 & 9/5
• B wt – 2.17 Kg
• Mom – 17 yr old primi, smoker
• Normal AN scans, serology negative, rubella
immune
• No risk factors
• No resuscitation needed at birth
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4. • Admitted to NNU from PN ward at 9 hrs of life
due to poor feeding, BM 1.6, Temp 35.6 &
respiratory distress
• O/A – no sucking, jittery, RR 72/mt, saturation
>94% in air, CRT <2 sec
• After sepsis work up, started on Pen+ Gent &
D10
• CXR – s/o TTN
• Gas –pH 7.35, PCO2 5.9, BE -4
• RD settled in 24 hours
• BM improved, started on oral feeds
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5. • Day 3 – Temp instability (37.5 – 37.3), brownish
reddish stool, abdominal distension
• Gastric aspirate 20 ml, non-bilious
• Sepsis work up repeated, NPO, IVF
• Antibiotics - ampicillin, cefotaxime & metronidazole
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6. Lab results
Date 5/9/05 6/9/05 8/9/05
WCC 10.1 5.26 1.95
Neut 5.7 3.5 0.55
Hb 16 16.9 14.6
Plt 233 202 184
Na 140 136 133
K 4 4.9 4.6
Urea 2.5 1.9 2.9
Creat 101 99 68
CRP <8 <8 61
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9. Diagnosis - NEC
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10. Introduction
• Necrotizing Enterocolitis (NEC) is the most common
gastrointestinal medical and/or surgical emergency
occurring in neonates
• Mortality rates approaching 50% in infants who weigh less
than 1500 g
• More common in premature infants, but also be observed
in term babies
• Despite intensive study over the past 30 years, its aetiology
remains elusive
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11. • NEC occur in three group of babies
• Term babies with risk factors
• < 30 weeks with no risk factors
• 30 - 36 weeks with asphyxia or
IUGR
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12. • NEC – the common end point precipitated by
different circumstances
• Prematurity
• IUGR
• PROM
• abruption
• asphyxia
• PDA
• Non human milk
• Bacterial infection
• Polycythemia
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13. Aetiology
• Multifactorial
• Prematurity
• Gut hypoxia
• Poor mucosal integrity
• Bacterial flora
• Klebsiella, E coli, enterobacter, clostridia
• Presence of metabolic substrate (milk) in the
lumen of gut
• Ischemia and/or reperfusion injury
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14. Path physiology
• NEC affects the gastrointestinal tract and, in
severe cases, can have profound systemic
impact
• Initial GI symptoms may be subtle:
 Feeding intolerance
 Delayed gastric emptying
 Abdominal distension and/or tenderness
 Ileus/decreased bowel sounds
 Abdominal wall erythema (advanced stages)
 Hematochezia
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15. Systemic signs:
 Apnoea
 Lethargy
 Decreased peripheral perfusion
 Shock (in advanced stages)
 Cardiovascular collapse
 Bleeding diathesis (consumption coagulopathy)
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16. Non-specific laboratory abnormalities:
o Hyponatremia
 Metabolic acidosis
 Thrombocytopenia
 Leukopenia and leukocytosis with left shift
 Neutropenia
 Prolonged prothrombin time (PT) and activated
partial thromboplastin time (APTT), decreasing
fibrinogen, rising fibrin split products (in cases of
consumption coagulopathy)
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17. Incidence
• 0.3-2.4 cases per 1000 live births
• 2-5% in VLBW
• 12% in Term babies
• Frequency varies from nursery to nursery without
correlation with season or geographic location
• Outbreaks of NEC seem to follow an epidemic
pattern within nurseries, suggesting an infectious
aetiology even though a specific causative
organism is unknown
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18. Clinical presentation
Term babies
 Typically the term baby is much younger than the
afflicted preterm baby, median age of onset from
1-3 days of life
 The affected term neonate is usually systemically ill
with other conditions, such as birth asphyxia,
respiratory distress, congenital heart disease,
metabolic abnormalities, or has a history of
abnormal foetal growth pattern.
 Maternal risk factors that reduce foetal gut flow,
such as placental insufficiency from chronic disease
or maternal cocaine abuse, can increase the
baby's risk
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19. Preterm Babies
 Premature babies are at risk for several weeks, with the age of
onset inversely related to gestational age at birth.
 Patients are typically advancing on enteral feedings or may
have achieved full-volume feeds when symptoms develop.
 Presenting symptoms may include subtle signs of feeding
intolerance that progress over several days, subtle systemic
signs that may be reported enigmatically by the nursing staff
as "acting different," and fulminant systemic collapse.
 Symptoms of feeding intolerance can include abdominal
dissention/tenderness, delayed gastric emptying as
evidenced by gastric residuals, and vomiting
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20.  Increased apnoea and bradycardia, lethargy,
and temperature instability representing the
primary manifestation
 Patients with fulminant NEC present with
profound apnoea, rapid cardiovascular and
haemodynamic collapse, and shock
 The baby's feeding history can help increase the
index of suspicion for early NEC. Babies who are
breastfed have a lower incidence of NEC than
formula-fed babies
 Rapid advancement of formula feeding has
been associated with an increased risk of NEC
(McKeown, 1992)
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21. Physical Examination
GI signs
 Increased abdominal girth
 Visible intestinal loops
 Obvious abdominal distension and decreased bowel sounds
 Change in stool pattern
 Hematochezia
 A palpable abdominal mass
 Erythema of the abdominal wall
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22. Systemic signs
 Respiratory failure
 Decreased peripheral perfusion
 Circulatory collapse
 With insidious onset, the severity of derangement may be mild, whereas
patients with fulminant disease can present with severe clinical
abnormalities
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23. Differential Diagnosis
• Septicaemia
• GOER
• Malrotation
• Volvulus
• Hirschsprungs disease
• Meningitis
• UTI
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24. Work up
• FBC
• Blood culture
• U & Es
• Blood gas
• Abdominal X-rays
o AP
o Left lateral decubitus
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25. Abdominal X-ray
findings:
• Dilated bowel loops
• Thickened bowel wall
• Fixed dilated loop
• Scarce or absent intestinal gas
• Pneumatosis intestinalis:
• radiologic sign pathognomonic of NEC
• appears as a characteristic train-track
lucency configuration within the bowel wall
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26. Abdominal X-ray(contd)
• Abdominal free air:
o ominous and usually requires emergency surgical
intervention
• Portal gas
o subtle and transient finding
• Ascites
o late finding
• Left side down (left lateral) decubitus radiography
o allows the detection of intraperitoneal air, which rises
above the liver shadow (right side up) and can be
visualized easier than on other views
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Pneumatosis intestinalis

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Portal venous air

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Penumoperitonium

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Left lateral decubitus radiograph shows free air

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Resected portion of necrotic bowel

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Normal (top) versus necrotic section of bowel

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Gut mucosal section showing transmural
necrosis

37. Other investigations
• Abdominal ultrasonography:
o The orientation of the superior mesenteric artery in relationship to
the superior mesenteric vein can provide information regarding
the possibility of a malrotation with a subsequent volvulus
o Doppler study of the splanchnic arteries
• Upper GI (with or without) small bowel follow-through
o a definitive way to diagnose the presence or absence of
intestinal volvulus
o Always consider intestinal volvulus if bilious vomiting is present,
especially in the term infant
o Volvulus being a surgical emergency, it is an important diagnosis
to exclude in a neonate with abdominal symptoms
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38. • Contrast enema
 a definitive way to diagnose a distal obstruction
 Always use a water-soluble contrast agent because of the
risk of perforation
 Contrast enemas are contraindicated in the presence of
perforation
 Consider carefully the clinical risks and benefits before
undertaking this evaluation in the unstable and/or acutely
ill infant
 Contrast enema findings are important for the differential
diagnosis of intestinal abnormalities because distal
obstructions, such as meconium plug, small left colon
syndrome, and Hirschsprung disease, may cause symptoms
in the baby without fulminant systemic collapse
 Rectal biopsy
 This procedure is the criterion standard for diagnosing
Hirschsprung disease
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39. Mortality & Morbidity
• Extremely premature infants (1000 g) are particularly
vulnerable, with reported mortality rates of 40-100%
• The mortality rate in infants weighing less than 1500
g 10-44%
• 0-20% for babies weighing more than 2500 g
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40. Morbidity
• Significant short-term and long-term morbidities:
• Depending on the location and extent of the bowel
removed, long-term morbidities:
o the need for colostomy
o repeated surgical procedures
o prolonged parenteral nutrition
o poor nutrition
o malabsorption syndromes
o failure to thrive
o multiple hospitalizations
o Strictures
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41. Bell Staging of NEC
NEC
Stage I
Suspected NEC
Stage IA Stage I B
Stage II
Definite NEC
Stage II A Stage II B
Stage III
Advanced NEC
Stage III A
Stage III B
Perforation
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42. Management
Based on stage of NEC
• Bell stage I - Suspected disease
o Stage IA
• Mild nonspecific systemic signs such as apnea,
bradycardia, and temperature instability
• Mild intestinal signs such as increased gastric
residuals and mild abdominal distention
• Radiographic findings can be normal or can show
some mild nonspecific distention
• Treatment - NPO with antibiotics for 3 days.
o Stage IB
• Diagnosis is the same as IA, with the addition of
grossly bloody stool.
• Treatment - NPO with antibiotics for 3 days
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43. Bell stage II - Definite disease
 Stage IIA
 Patient is mildly ill
 Diagnostic signs include the mild systemic signs
present in stage IA
 Intestinal signs include all of the signs present in stage
I, with the addition of absent bowel sounds and
abdominal tenderness
 Radiographic findings show ileus and/or pneumatosis
intestinalis. This diagnosis is sometimes referred to
colloquially as medical NEC
 Treatment includes NPO and antibiotics for 7-10 days
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44. Stage IIB
 Patient is moderately ill.
 Diagnosis requires all of stage I signs plus the systemic
signs of moderate illness, such as mild metabolic
acidosis and mild thrombocytopenia.
 Abdominal examination reveals definite tenderness,
perhaps some erythema or other discoloration,
and/or right lower quadrant mass.
 Radiographs show portal venous gas with or without
ascites.
 Treatment - NPO and antibiotics for 14 days
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45. Bell stage III - Represents advanced NEC with severe illness
that has a high likelihood of progressing to surgical
intervention
 Stage IIIA
 Patient has severe NEC with an intact bowel
 Diagnosis requires all of the above conditions, with the addition
of hypotension, bradycardia, respiratory failure, severe
metabolic acidosis, coagulopathy, and/or neutropenia
 Abdominal examination shows marked distension with signs of
generalized peritonitis
 Radiographic examination reveals definitive evidence of
ascites
 Treatment involves NPO for 14 days, fluid resuscitation, inotropic
support, ventilator support, and paracentesis
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46. Stage IIIB
 severely ill infant with perforated bowel on
radiograph
 Free air visible on abdominal radiograph -
indicates surgical intervention
 Surgical treatment:
 Resection of the affected portion of the bowel, which may be
extensive
 Initially, an ileostomy with a mucous fistula is typically performed, with
reanastomosis performed later
 Strictures may occur, with or without a history of surgical intervention,
which may require surgical treatment
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47. Supportive Management
• NPO
• IVF
• Antibiotics
o vancomycin, cefotaxime, and clindamycin or
metronidazole
• Antifungal
o Fluconazole
• Vasopressors
• Albumin
• Prolonged parenteral nutrition
• Prolonged broad-spectrum antibacterial therapy
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48. Complication
• Approximately 75% of all patients
survive
• Of those patients who survive, 50%
develop a long-term complication
• intestinal stricture
• short-gut syndrome
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49. Intestinal strictures
 Can develop in infants with or without a
preceding perforation
 Incidence 25-33%
 Strictures most commonly involve the left side of
the colon
 Symptoms of feeding intolerance and bowel
obstruction typically occur 2-3 weeks after
recovery from the initial event
 Presence and location of the obstruction is
diagnosed using barium enema; surgical
resection of the affected area is required
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50. Short-gut syndrome
 Malabsorption syndrome resulting from removal
of excessive/critical portions of small bowel
necessary for absorption essential nutrients from
intestinal lumen
 Symptoms most profound in babies who either
have lost most of their small bowel or have lost
a smaller portion that includes the ileocecal
valve
 Loss of small bowel can result in malabsorption
of nutrients as well as fluids and electrolytes
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51. Prevention
• Term babies:
• prevention of asphyxia
• slow introduction of feeds
• Preterm:
• antenatal steroids
• Breast milk feeds
• avoid hyperosmolar feeds
• avoid rapid increase of feeds
• control infection
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52. • Breastfed babies have a lower incidence of NEC than
formula-fed babies (Lucas, 1990; Eyal, 1982)
• Role of feeding regimens in the aetiology of NEC
o Clinical research does not demonstrate definitive
evidence for either causation or prevention
o In 1992, McKeown et al reported that rapid increase in
feeding volume (>20 mL/kg/d) was associated with
higher risk of NEC
o In 1999, Rayyis et al showed no difference in NEC Bell
stage greater than or equal to II in patients advanced at
15 mL/kg/d compared with those advanced at 35
mL/kg/d
o Systematic review published by the Cochrane
Collaboration in 1999 reported no effect on NEC of rapid
feeding advancement for low–birth weight infants
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53. Cochrane reviews
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54. Arginine supplementation for prevention of
necrotising enterocolitis in preterm infants
Shah P, Shah V.
The Cochrane Database of Systematic Reviews 2004
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55. • Objectives: This review examines the efficacy and
safety of arginine supplementation in decreasing
the incidence of NEC among preterm neonates
• Search:
• MEDLINE (1966 - June 2004)
• EMBASE (1980 - June 2004)
• CINAHL (1982 - June 2004)
• Cochrane Controlled Trials Register (Issue 2, 2004 of Cochrane Library)
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56. • Selection criteria: Study design: randomized or
quasi-randomized controlled trials
• Population: preterm neonates
• Intervention: enteral or parenteral arginine
supplementation (in addition to what an infant
may be receiving from enteral or parenteral
source), compared to placebo or no treatment;
arginine administered orally or parenterally for at
least 7 days in order to achieve adequate plasma
arginine levels (145 umol/l).
• Outcomes: any of the following outcomes - NEC,
death prior to discharge, death due to NEC,
surgery for NEC, duration of total parenteral
nutrition
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57. • Main results: a statistically significant reduction in
the risk of developing NEC (any stage) in the
arginine group compared with the placebo
group (RR 0.24 [95% CI 0.10, 0.61], RD -0.21 [95% CI -0.32, -0.09]).
No significant side effects directly attributable to
arginine were observed.
• Authors' conclusions: The data are insufficient at
present to support a practice recommendation.
A multicentre randomized controlled study of
arginine supplementation in preterm neonates is
needed, focusing on the incidence of NEC,
particularly stage 2 or 3
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58. Enteral antibiotics for preventing
necrotizing enterocolitis in low birth
weight or preterm infants
(Cochrane Review)
Bury RG, Tudehope D
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59. • Objectives: To evaluate the benefits and harms
of enteral antibiotic prophylaxis for necrotizing
enterocolitis in low birth weight and preterm
infants
• Selection criteria: All randomized or quasi-
randomized controlled trials where enteral
antibiotics were used as prophylaxis against
NEC in LBW (<2500g) and/or preterm (<37
weeks gestation) infants
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60. • Main results:
o Five eligible trials involving 456 infants.
o The administration of prophylactic enteral
antibiotics resulted in a statistically significant
reduction in NEC
o [RR 0.47 (0.28, 0.78); RD -0.10 (-0.16, -0.04); NNT
10 (6, 25)]
o There was a statistically significant reduction in
NEC-related deaths [RR 0.32 (0.10, 0.96); RD -
0.07 (-0.13, 0.01); NNT 14 (8, 100)]
• Authors' conclusions: Evidence suggests that oral
antibiotics reduce the incidence of NEC in low
birth weight infants
• However concerns about adverse outcomes
persist, particularly related to the development of
resistant bacteria
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61. Oral immunoglobulin for preventing
necrotizing enterocolitis in preterm and
low birth-weight neonates
(Cochrane Review)
Foster J, Cole M
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62. • Objectives: To assess whether oral
immunoglobulin administered to preterm and
low birth-weight neonates reduces the
incidence of necrotizing enterocolitis without
adverse effects
• Selection criteria: All randomized or quasi-
randomized controlled trials where oral
immunoglobulins were used as prophylaxis
against necrotizing enterocolitis in preterm
(<37 weeks gestation) and/or low birth-weight
(<2500 gms) neonates
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63. • Three eligible trials (including a total of 2095
neonates) the oral administration of IgG or an
IgG/IgA combination did not result in a
significant reduction in the incidence of definite
NEC [RR 0.84 (95% CI 0.57, 1.25), suspected NEC
[RR 0.84 (95% CI 0.49, 1.46), need for surgery [RR
0.21 (95% CI 0.02, 1.75), or death from NEC [RR
1.10 (95% CI 0.47, 2.59)
• Authors' conclusions: Based on the available
trials, the evidence does not support the
administration of oral immunoglobulin for the
prevention of NEC D 0.00 (95% CI -0.01, 0.01)].
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64. Umbilical artery catheters in the
newborn: effects of position of the
catheter tip
(Cochrane Review)
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65. • Objectives: To determine whether the position of
the tip of an umbilical arterial catheter influences
the frequency of ischemic events, aortic
thrombosis, intraventricular hemorrhage, mortality
or necrotising enterocolitis in newborn infants
• Selection criteria: Randomized trials in newborn
infants of any birthweight or gestation.
Comparison of high catheter placement with the
tip above the diaphragm to a lower position just
above the aortic bifurcation. Clinically important
end points such as ischemic events or aortic
thrombosis
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66. • Main results: High placed umbilical artery
catheters are associated with a lower
incidence of clinical vascular complications,
without an increase in any adverse sequelae.
Intraventricular hemorrhage rates, death and
necrotising enterocolitis are not more frequent
with high compared to low catheters.
• Authors' conclusions: There appears to be no
evidence to support the use of low placed
umbilical artery catheters. High catheters
should be used exclusively
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67. Rapid versus slow rate of advancement of
feedings for promoting growth and
preventing necrotizing enterocolitis in
parenterally fed low-birth-weight infants
(Cochrane Review)
Kennedy KA, Tyson JE
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68. • Objectives: For low birth weight or premature
infants receiving parenteral nutrition, to assess the
effect of different rates of advancement of
enteral feedings beginning at the same age on
measures of feeding tolerance and neonatal
outcome
• Main results: Among infants randomized to more
rapid rates of advancement of feedings, there
was an overall reduction in days to full enteral
feeding and days to regain birth weight. There
was no significant effect on necrotizing
enterocolitis (relative risk = 0.97, 95% confidence
interval = 0.50, 1.87)
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69. Authors' conclusions:
• There are suggested advantages of more rapid
rates of advancing feedings in premature low-
birth-weight infants (shorter time to regain birth
weight and shorter time to achieve full feedings)
• It is unclear whether this strategy should be
adopted as routine practice because of limited
information regarding safety
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70. Thank you