3. PATIENT BASIC DATA
Name :林○彤
Gender: F, twin A
GA: 25+3 weeks , BBW: 438g via C/S
Chart number: 42692740
Admission date: 2015/10/22~ now
4. AFTER BIRTH…
Extremely prematurity
Poor crying and activity
severe substernal, intercostal retraction were
noted
Admitted for further evaluation & treatment
14. 12/02
Abdominal distention progressed, especially right
upper quadrate, mild dark skin color, no heat
sensation or pulsation noted
no stool passage note
Bedside sono: showed a 2x2 mass noted at RUQ,
intussusception is less likely
consult PEDS doctor
15. Try OG feeding 2c.c. water-soluable
contrast follow up KUB tomorrow
afternoon
12/03
Prescribed oral contrast in the morning
KUB at 12/3 4 pm:
some oral contrast still in stomach and
intestinal
KUB on 12/4 morning:
no contrast in stomach and much
improve than previous KUB
23. Necrotizing enterocolitis is the most common and
devastating disease among neonates and has
become a priority for research because it’s
difficult to eradicate.
It was first described before 1960, but the entity
was not recognized until after the advent of
modern neonatal intensive care.
Since that time, the incidence of necrotizing
enterocolitis and the associated morbidity and
mortality have remained unchanged because of
ever-improving survival of the smallest infants.
24. Necrotizing enterocolitis is the most common and
devastating disease among neonates and has
become a priority for research because it’s
difficult to eradicate.
It was first described before 1960, but the entity
was not recognized until after the advent of
modern neonatal intensive care.
Since that time, the incidence of necrotizing
enterocolitis and the associated morbidity and
mortality have remained unchanged because of
ever-improving survival of the smallest infants.
25. Necrotizing enterocolitis is the most common and
devastating disease among neonates and has
become a priority for research because it’s
difficult to eradicate.
It was first described before 1960, but the entity
was not recognized until after the advent of
modern neonatal intensive care.
Since that time, the incidence of necrotizing
enterocolitis and the associated morbidity and
mortality have remained unchanged because of
ever-improving survival of the smallest infants.
26. The mean prevalence of the disorder is about 7%
among infants with a birth weight between 500
and 1500 g.
The estimated rate of death associated with
necrotizing enterocolitis ranges between 20 and
30%, with the highest rate among infants
requiring surgery.
On the basis of large, multicenter, neonatal network
databases from the United States and Canada
27. The mean prevalence of the disorder is about 7%
among infants with a birth weight between 500
and 1500 g.
The estimated rate of death associated with
necrotizing enterocolitis ranges between 20 and
30%, with the highest rate among infants
requiring surgery.
On the basis of large, multicenter, neonatal network
databases from the United States and Canada
28. The excessive inflammatory process initiated in
the highly immunoreactive intestine in
necrotizing enterocolitis extends the effects of the
disease systemically, affecting distant organs
such as the brain and placing affected infants at
substantially increased risk for
neurodevelopmental delays.
An infant recovering from necrotizing
enterocolitis may have nearly a 25% chance of
microcephaly and serious neurodevelopmental
delays that will transcend concerns that pertain
to the gastrointestinal tract.
29. The excessive inflammatory process initiated in
the highly immunoreactive intestine in
necrotizing enterocolitis extends the effects of the
disease systemically, affecting distant organs
such as the brain and placing affected infants at
substantially increased risk for
neurodevelopmental delays.
An infant recovering from necrotizing
enterocolitis may have nearly a 25% chance of
microcephaly and serious neurodevelopmental
delays that will transcend concerns that pertain
to the gastrointestinal tract.
30. The total annual estimated cost of caring for
affected infants in the United States is between
$500 million and $1 billion.
Infants with necrotizing enterocolitis were
hospitalized 60 days longer than unaffected
preterm infants if surgery was required and more
than 20 days longer if surgery was not necessary.
Bowel resection is the most severe complication
and major cause of the short-bowel disease.
The total mean cost of care over a 5-year period
for a child with the short-bowel syndrome has
been estimated to be nearly $1.5 million.
31. The total annual estimated cost of caring for
affected infants in the United States is between
$500 million and $1 billion.
Infants with necrotizing enterocolitis were
hospitalized 60 days longer than unaffected
preterm infants if surgery was required and more
than 20 days longer if surgery was not necessary.
Bowel resection is the most severe complication
and major cause of the short-bowel disease.
The total mean cost of care over a 5-year period
for a child with the short-bowel syndrome has
been estimated to be nearly $1.5 million.
32. The total annual estimated cost of caring for
affected infants in the United States is between
$500 million and $1 billion.
Infants with necrotizing enterocolitis were
hospitalized 60 days longer than unaffected
preterm infants if surgery was required and more
than 20 days longer if surgery was not necessary.
Bowel resection is the most severe complication
and major cause of the short-bowel disease.
The total mean cost of care over a 5-year period
for a child with the short-bowel syndrome has
been estimated to be nearly $1.5 million.
33. The total annual estimated cost of caring for
affected infants in the United States is between
$500 million and $1 billion.
Infants with necrotizing enterocolitis were
hospitalized 60 days longer than unaffected
preterm infants if surgery was required and more
than 20 days longer if surgery was not necessary.
Bowel resection is the most severe complication
and major cause of the short-bowel disease.
The total mean cost of care over a 5-year period
for a child with the short-bowel syndrome has
been estimated to be nearly $1.5 million.
35. However, the most typical initial signs and
symptoms of “classic” necrotizing enterocolitis in
a preterm infant include feeding intolerance,
abdominal distention, and bloody stools after 8 to
10 days of age.
The pathognomonic findings on abdominal
radiography are pneumatosis intestinalis, portal
venous gas, or both.
36.
37. Early imaging signs that should raise the
suspicion of necrotizing enterocolitis include
dilated loops of bowel, a paucity of gas, and gas-
filled loops of bowel that are unaltered on
repeated examinations.
Extraluminal air (“free air”) outside the bowel is
a sign of advanced necrotizing enterocolitis.
38. Symptoms may progress rapidly, often within
hours, from subtle signs to abdominal
discoloration, intestinal perforation, and
peritonitis, leading to systemic hypotension that
requires intensive medical support, surgical
support, or both.
39. Because of the lack of clear delineation of what
constitutes the diagnosis of classic NEC, the term
“necrotizing enterocolitis” often reflects a
spectrum of intestinal conditions that differ with
respect to pathogenesis and the strategies
required for prevention and treatment.
Three forms of neonatal intestinal injury occur
most often: conditions primarily seen in term
infants, spontaneous intestinal perforations, and
classic necrotizing enterocolitis.
40. CONDITIONS PRIMARILY SEEN IN TERM INFANTS
The disease usually occurs in the first week after
birth, but it differs from that seen in preterm
infants in that it is more often associated with
other problems, such as maternal illicit drug use,
intestinal anomalies (e.g., aganglionosis or
atresias), congenital heart disease, and perinatal
stress that may affect mesenteric blood flow.
41. SPONTANEOUS INTESTINAL PERFORATIONS
Spontaneous intestinal perforation usually occurs
in the first several days after birth and is not
associated with enteral feeding.
This disorder is characterized by only minimal
intestinal inflammation and necrosis, as
evidenced by low levels of serum inflammatory
cytokines.
It has been associated with the administration of
indomethacin and with glucocorticoids such as
dexamethasone or hydrocortisone.
42. CLASSIC NECROTIZING ENTEROCOLITIS
A systematic description of necrotizing
enterocolitis, the staging system described by
Bell et al., was first published in 1978 and
subsequently refined.
43. Stage 1 criteria are highly nonspecific findings
and may include feeding intolerance, mild
abdominal distention, or both.
Stage 2 criteria are radiographic findings such as
pneumatosis intestinalis, which may be hard to
detect on radiographs.
One of the most important criteria for stage 3 is a
perforated viscus, which may or may not be
associated with intestinal necrosis and which
could, in fact, be a spontaneous intestinal
perforation or dissected air from the pleural
cavity.
44. Stage 1 criteria are highly nonspecific findings
and may include feeding intolerance, mild
abdominal distention, or both.
Stage 2 criteria are radiographic findings such as
pneumatosis intestinalis, which may be hard to
detect on radiographs.
One of the most important criteria for stage 3 is a
perforated viscus, which may or may not be
associated with intestinal necrosis and which
could, in fact, be a spontaneous intestinal
perforation or dissected air from the pleural
cavity.
45. Stage 1 criteria are highly nonspecific findings
and may include feeding intolerance, mild
abdominal distention, or both.
Stage 2 criteria are radiographic findings such as
pneumatosis intestinalis, which may be hard to
detect on radiographs.
One of the most important criteria for stage 3 is a
perforated viscus, which may or may not be
associated with intestinal necrosis and which
could, in fact, be a spontaneous intestinal
perforation or dissected air from the pleural
cavity.
46.
47.
48.
49.
50.
51. Another classification system used to define
necrotizing enterocolitis more specifically is
published in the Vermont Oxford Network
Manual of Operations.
This manual describes clinical and radiographic
findings, with one or more of each type of finding
(clinical or radiographic) required to establish a
diagnosis of necrotizing enterocolitis.
52. The clinical findings include bilious gastric
aspirate or emesis, abdominal distention, and
occult gross blood in the stool, with the absence of
anal fissures.
The imaging findings include pneumatosis
intestinalis, hepatobiliary gas, and
pneumoperitoneum.
53. The clinical findings include bilious gastric
aspirate or emesis, abdominal distention, and
occult gross blood in the stool, with the absence of
anal fissures.
The imaging findings include pneumatosis
intestinalis, hepatobiliary gas, and
pneumoperitoneum.
54. Both Bell staging and Vermont-Oxford diagnostic
approach has similar shortcomings that severe
necrotizing enterocolitis requiring surgery can
develop in patients even though pneumatosis
intestinalis or portal gas has not been detected on
imaging.
These patients may only have abdominal
distention, without intraluminal bowel gas, on
presentation.
Thus, the ominous progression of the disease may
be missed, with a failure to intervene early
enough.
55. A more reliable staging approach that allows for
aggressive preventive measures is needed, but it
will probably require the development of
biomarkers that accurately predict the full
expression of necrotizing enterocolitis.
57. Almost all very-low-birth-weight infants have
intermittent gastrointestinal symptoms that may
cause concern, but most do not have necrotizing
enterocolitis.
Definitive necrotizing enterocolitis may require
medical or surgical management based on the
clinical presentation.
58. Medical intervention typically includes
abdominal decompression, bowel rest, broad-
spectrum intravenous antibiotics, and
intravenous hyperalimentation.
Surgical interventions are generally required in
patients with intestinal perforation or
deteriorating clinical or biochemical status (e.g.,
shock or a decreasing platelet count, neutrophil
count, or both).
Surgicalprocedures may involve drain placement,
exploratory laparotomy with resection of diseased
bowel, and enterostomy with creation of a stoma.
59. Medical intervention typically includes
abdominal decompression, bowel rest, broad-
spectrum intravenous antibiotics, and
intravenous hyperalimentation.
Surgical interventions are generally required in
patients with intestinal perforation or
deteriorating clinical or biochemical status (e.g.,
shock or a decreasing platelet count, neutrophil
count, or both).
Surgicalprocedures may involve drain placement,
exploratory laparotomy with resection of diseased
bowel, and enterostomy with creation of a stoma.
60. Medical intervention typically includes
abdominal decompression, bowel rest, broad-
spectrum intravenous antibiotics, and
intravenous hyperalimentation.
Surgical interventions are generally required in
patients with intestinal perforation or
deteriorating clinical or biochemical status (e.g.,
shock or a decreasing platelet count, neutrophil
count, or both).
Surgicalprocedures may involve drain placement,
exploratory laparotomy with resection of diseased
bowel, and enterostomy with creation of a stoma.
61. LAPAROTOMY VS PERITONEAL DRAINAGE
Two commonly used methods for treating
advanced necrotizing enterocolitis with intestinal
perforation are laparotomy and primary
peritoneal drainage without laparotomy.
Two large multicenter studies concluded that the
type of procedure does not influence survival or
other clinically important early outcomes.
The second study also showed that infants
treated with peritoneal drainage very often
required a subsequent laparotomy.
Further analysis of the latter study showed no
immediate clinical status improvement when
peritoneal drainage was used for this purpose.
62. LAPAROTOMY VS PERITONEAL DRAINAGE
Two commonly used methods for treating
advanced necrotizing enterocolitis with intestinal
perforation are laparotomy and primary
peritoneal drainage without laparotomy.
Two large multicenter studies concluded that the
type of procedure does not influence survival or
other clinically important early outcomes.
The second study also showed that infants
treated with peritoneal drainage very often
required a subsequent laparotomy.
Further analysis of the latter study showed no
immediate clinical status improvement when
peritoneal drainage was used for this purpose.
63. LAPAROTOMY VS PERITONEAL DRAINAGE
Two commonly used methods for treating
advanced necrotizing enterocolitis with intestinal
perforation are laparotomy and primary
peritoneal drainage without laparotomy.
Two large multicenter studies concluded that the
type of procedure does not influence survival or
other clinically important early outcomes.
The second study also showed that infants
treated with peritoneal drainage very often
required a subsequent laparotomy.
Further analysis of the latter study showed no
immediate clinical status improvement when
peritoneal drainage was used for this purpose.
64. LAPAROTOMY VS PERITONEAL DRAINAGE
Two commonly used methods for treating
advanced necrotizing enterocolitis with intestinal
perforation are laparotomy and primary
peritoneal drainage without laparotomy.
Two large multicenter studies concluded that the
type of procedure does not influence survival or
other clinically important early outcomes.
The second study also showed that infants
treated with peritoneal drainage very often
required a subsequent laparotomy.
Further analysis of the latter study showed no
immediate clinical status improvement when
peritoneal drainage was used for this purpose.
65. A systematic review of several studies suggested
mortality was increased by more than 50% with
peritoneal drainage as compared with
laparotomy.
Follow-up examinations at 18 to 22 months in
infants who had undergone surgery for
necrotizing enterocolitis in the neonatal period
showed a significantly reduced risk of death or
neurodevelopmental impairment among those
who had undergone a laparotomy as compared
with those who had undergone peritoneal
drainage.
66. A systematic review of several studies suggested
mortality was increased by more than 50% with
peritoneal drainage as compared with
laparotomy.
Follow-up examinations at 18 to 22 months in
infants who had undergone surgery for
necrotizing enterocolitis in the neonatal period
showed a significantly reduced risk of death or
neurodevelopmental impairment among those
who had undergone a laparotomy as compared
with those who had undergone peritoneal
drainage.
67. These studies indicate that once surgery is
required, the outcome may be poor, a finding that
underscores the need for effective prevention.
75. INTESTINAL IMMATURITY
Excessive inflammatory response
Preterm baby against luminal
microbial stimuli ↑, and alter barrier
in the intestine
TLR4↑, IkB and NF-kB↓ (fetus v.s. adult)
Cytokine , IL-8↑ necrosis and
production of acute-phase protein in
the gut↑
Enterocytes of preterm baby are not
prepared for the excessive stimulation
of initial postnatal colonization
76. MICROBIAL COLONIZATION
Inappropriate microbial colonization
Preterm baby NEC occurs until 8-10
days post partum
Experiment: NEC do not occur in
germ-free animals
NEC baby always has bacteremia and
endotoxemia
77. MICROBIAL COLONIZATION
Preliminary studies
Groups:
→unusual intestinal microbial species
and diversity of microbial species↓
Commensal bacteria evoke excessive
inflammation in fetal enterocyte
(related to IkB↓)
Unaffected
preterm
baby
Infants who
developed
NEC
Infants who
before or
during NEC
79. HYPOXIA-ISCHEMIA Downstream role in NEC
Modulation of microvascular tone
imbalance
Vascular regulators :
1.nitric oxide
2.endothelin
80. OTHER CONTRIBUTING
FACTORS Blood transfusion
The way to blood transfusion
→ hypoxia-ischemia problem
Not association with pathogenesis of
NEC
Use of umbilical catheters
Parental nutrition via an umbilical-
artery catheter
82. MEASURES TO PREVENT NECEvidence of
efficacy and safety
Evidence of
efficacy but
questionable
safety
Evidenced of efficacy
in animals models
but not in humans
Proposed efficacy
but lacking
evidence
Breast-milk feeding
Enteral
aminoglycosides
Anti-cytokines
Prebiotics (derived
from plants and
breast milk)
Probiotics
Microbial
components and
TLR agonists
Nonaggressive
enteral feeding
Glucocorticoids
Growth factors
Glutamine, n-3
fatty acidsArginine
83. ENTERAL FEEDING After withholding enteral feeding, rapid
increase in feeding cause NEC↑
Complete withholding of feeding is
dangerous practice
Prolonged use of parenteral nutrition
Intestinal atrophy
Permeability and inflammation↑
Late-onset sepsis↑
→Delay feeding increases NEC
severity
84. ENTERAL FEEDING Provide enteral feeding of mother’s
expressed breast milk to prevent NEC
Human milk + human milk-derived fortifier
→ low incidence of NEC
85. MEASURES TO PREVENT NECEvidence of
efficacy and safety
Evidence of
efficacy but
questionable
safety
Evidenced of efficacy
in animals models
but not in humans
Proposed efficacy
but lacking
evidence
Breast-milk feeding
Enteral
aminoglycosides
Anti-cytokines
Prebiotics (derived
from plants and
breast milk)
Probiotics
Microbial
components and
TLR agonists
Nonaggressive
enteral feeding
Glucocorticoids
Growth factors
Glutamine, n-3
fatty acidsArginine
86. ENTERAL AMINOGLYCOSIDES May be efficacy but NICU avoid the
practice
→ resistant microorganisms often emerge
Empirical use of IV antibiotics
→ NEC incidence increased
87. PROBIOTICS NEC incidence↓
Mortality of NEC did not decreased
Incidence of sepsis ↑
Birth weight < 750g
Commentary suggesting the routine use
of probiotics, but FDA hasn’t approved
in preterm baby
Not rigorous manufacturing quality
control of probiotics
88. MEASURES TO PREVENT NECEvidence of
efficacy and safety
Evidence of
efficacy but
questionable
safety
Evidenced of efficacy
in animals models
but not in humans
Proposed efficacy
but lacking
evidence
Breast-milk feeding
Enteral
aminoglycosides
Anti-cytokines
Prebiotics (derived
from plants and
breast milk)
Probiotics
Microbial
components and
TLR agonists
Nonaggressive
enteral feeding
Glucocorticoids
Growth factors
Glutamine, n-3
fatty acidsArginine
89. PREBIOTICS Can enhance growth of potential beneficial
intestinal microbes
Include oligosaccharides inulin, galactose,
fructose, lactulose, and combinations
Functions
Alter consistency and frequency of stools
Enhance proliferation of endogenous flora
→Bifidobacteria (lack in very-low-birth-
weight preterm infants)
Prevention of NEC is unclear！
90. MICROBIAL COMPONENTS THAT
MODULATE INFLAMMATION
Dead microbes are also effective in
modulating excessive inflammatory stimuli
Mouse model studies about IRAK-1
Intestinal epi. has high lipopolysaccharide
reactivity in the fetus, and decreased
through vaginal birth
If delivered by CS, IRAK-1 expression is
not decreased, which continue to respond to
lipopolysaccharide →intestinal
inflammation and injury↑
91. MICROBIAL COMPONENTS THAT
MODULATE INFLAMMATION
Expression of TLR-4 is the pathogenesis of
NEC！
Preterm infants with NEC have higher
TLR4 than full-term infants
TLR4 expression increases NEC and
intestinal inflammation
Location of TLR4 on the surface of intestine
may limit activation by colonizing bacteria
Alter the accessibility of colonizing bacteria
to TLRs can be therapeutic potential
