Transcript New Ideas in the Nutrition of the ELBW Infant Reese H Clark, MD.

New Ideas in the Nutrition of the
ELBW Infant
Reese H Clark, MD
1
• I have no conflicts of interest to report
• I will not be discussing the off label use of any
medications.
2
Goals
• To challenge conventional thinking on
nutrition in the NICU
• To encourage earlier use of enteral nutrition
• To show that exclusive of human milk as a
nutritional support can safely promote good
growth of preterm infants
3
GROWTH IS IMPORTANT
Real Important! Effects Everyone
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Outcomes of Small for Gestational Age Infants
Born at <27 Weeks' Gestation
Lilia C. De Jesus et al.
Journal of Pediatrics
DOI: 10.1016/j.jpeds.2012.12.097
5
6
Postnatal Growth Impacts Outcome
How growth is monitored and
supported in the NICU matters
7
Methods
• Infants 501 to 1000 g birth weight were divided into
quartiles of in-hospital growth velocity rates
• Variables considered for the logistic-regression
models included gender, race, gestational age, small
for gestational age, mother’s education, severe
intraventricular hemorrhage, periventricular
leukomalacia, age at regaining birth weight,
necrotizing enterocolitis, late-onset infection,
bronchopulmonary dysplasia, postnatal steroid
therapy for pulmonary disease, and center
Ehrenkranz RA et al. Pediatrics 2006:117:1253-61
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9
Head Growth
10
Percent of Patients with Outcome
Cerebral Palsy by
Weight Gain Quartile
25%
20%
15%
10%
5%
0%
12.0 (2.1)
15.6 (0.8)
17.8 (0.8)
21.2 (2)
Weight Gain Groups (grams/kg/day)
Ehrenkranz RA et al. Pediatrics 2006:117:1253-61
Growth in the NICU
12
Average body weight versus postmenstrual age in weeks for all study infants with
gestational ages 24 to 25 weeks (dotted line), 26 to 27 weeks (short dashes), and 28 to
29 weeks (long dashes)
Ehrenkranz R A et al. Pediatrics 1999;104:280-289
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©1999 by American Academy of Pediatrics
Slopes of postnatal growth in the NICU
Weight (kg)
Inborn Infants Who Survived, 26 weeks EGA (n=1000)
Based On Data in the Pediatrix Clinical Data Warehouse 2009-2010
2.2
2
1.8
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
Enteral
Phase
Transitional
Phase
Parenteral
Phase
24
25
26
27
28
29
30
31
32
33
34
35
36
Postmenstrual Age (weeks)
Copyright 2011 MEDNAX PSO, LLC
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Clark RH, Thomas P, Peabody J. Extrauterine growth restriction remains a
serious problem in prematurely born neonates. Pediatrics. 2003;111:986-990
EGA and birth weight remain the most important factors influencing postnatal
growth
15
Weight Z score
Birth vs Discharge
Median
10th
90th
1.5
1
0.5
0
-0.5
-1
-1.5
-2
-2.5
-3
32 (29116)
32 (29117)
31 (22020)
31 (22044)
30 (16374)
30 (16399)
29 (12165)
29 (12179)
28 (10125)
28 (10160)
27 (7476)
27 (7512)
26 (5645)
26 (5697)
25 (4265)
25 (4306)
24 (2587)
24 (2623)
23 (753)
23 (774)
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Length Z score
Birth vs Discharge
Median
10th
90th
2
1
0
-1
-2
-3
-4
32 (21286)
32 (27486)
31 (16615)
31 (20875)
30 (12399)
30 (15440)
29 (9180)
29 (11385)
28 (7701)
28 (9404)
27 (5684)
27 (6868)
26 (4334)
26 (5176)
25 (3262)
25 (3803)
24 (1969)
24 (2331)
23 (559)
23 (661)
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BMI (Weight/Length2)
Birth vs Discharge
Median
10th
90th
1.8
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
32 (21365)
32 (27500)
31 (16682)
31 (20884)
30 (12460)
30 (15450)
29 (9259)
29 (11394)
28 (7793)
28 (9414)
27 (5759)
27 (6878)
26 (4455)
26 (5184)
25 (3356)
25 (3810)
24 (2036)
24 (2337)
23 (585)
23 (664)
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Head Circumference Z score
Birth vs Discharge
Median
10th
90th
2
1.5
1
0.5
0
-0.5
-1
-1.5
-2
-2.5
-3
32 (25059)
32 (27860)
31 (19430)
31 (21220)
30 (14517)
30 (15750)
29 (10765)
29 (11591)
28 (8980)
28 (9628)
27 (6621)
27 (7060)
26 (5069)
26 (5349)
25 (3757)
25 (3960)
24 (2269)
24 (2436)
23 (664)
23 (702)
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Growth Assessment
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21
Nutrition
22
Median Total Calories (cal/kg/day)
Quantiles90
Quantiles10
Median
160
140
120
100
80
60
40
20
23 to 26 weeks
27 to 28 weeks
29 to 31 weeks
0
1
7
28
42
1
7
28 42
Days Since Birth
1
Factors that Influence Amino Acid and Acylcarnitine Profiles in Premature Infants
From The Pediatrix-Obstetrix Center for Research, Education and Quality
7
28
42
23
Parenteral Nutrition
24
25
Glucose
26
Glucose Infusion Rate (GIR)
• A GIR of 5-8 mg/kg/min is typical
• Infants who are not feeding should not be
allowed a rate less than 5 mg/kg/min for any
significant period of time
• The GIR needed to optimize nutrition in
neonates is 10-16 mg/kg/min
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Median Glucose Infusion (zero if not on fluids)
(grams/kg/day)
Quantiles90
18
16
14
12
10
8
6
4
2
0
23 to 26 weeks
1
7
Quantiles10
27 to 28 weeks
1
7
Days Since Birth
Median
29 to 31 weeks
1
7
28
Which of our patients is most at risk for poor
growth in the NICU?
Hypoglycemia
Hyperglycemia
Percent with Diagnosis
40%
35%
30%
25%
20%
15%
10%
5%
0%
23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41
EGA
Early Insulin Therapy in Very-Low-Birth-Weight Infants
• The early-insulin group had significantly more carbohydrate
infused (51±13 vs. 43±10 kcal/kg per day, P<0.001) and less
weight loss in the first week (standard-deviation score for
change in weight, −0.55±0.52 vs. −0.70±0.47; P = 0.006)
• More infants in the early-insulin group had episodes of
hypoglycemia (<47 mg/dl for >1 hour) Incidence was
– 29% in the early-insulin group
– 17% in the control group, P = 0.005
• In the intention-to-treat analysis, mortality at 28
days was higher in the early insulin group than in
the control group (P = 0.04).
Beardsall et al. N Engl J Med 2008;359:1873-84.
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Complications
Insulin
Control
35%
30%
25%
20%
15%
10%
5%
0%
Hypoglycemia
Death
Interventions for prevention of neonatal hyperglycemia
in very low birth weight infants.
• Four eligible trials
• Two trials compared lower vs. higher rates of glucose infusion
in the early postnatal period. These trials were too small to
assess effects on mortality or major morbidities.
• Two trials, one a moderately large multicentre trial (NIRTURE,
Beardsall 2008), compared insulin infusion with standard care.
• Insulin infusion reduced hyperglycemia but increased death
before 28 days and hypoglycemia
• Reduction in hyperglycemia was not accompanied by
significant effects on major morbidities; effects on
neurodevelopment are awaited
Sinclair JC et al. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD007615
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Amino Acids
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Clark RH, Chace DH, Spitzer AR. Pediatrics.
2007;120:1286-96.
• Randomly allocated premature (23-29 weeks and 6
days of gestation) neonates to
– amino acid supplementation started at 1.0 g/kg per day
and advanced by 0.5 g/kg per day to a maximum of 2.5
g/kg per day (2.5 g/kg per day group).
– Other group received amino acids starting at 1.5 g/kg per
day and advancing by 1.0 g/kg per day to a maximum of
3.5 g/kg per day (3.5 g/kg per day group)
• Enrolled 122 neonates
• Higher doses of amino acid supplementation did not
improve neonatal growth and were associated with
increased blood amino acid and urea nitrogen levels
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Burattini I, et al. Targeting 2.5 versus 4 g/kg/day of Amino Acids
for Extremely Low Birth Weight Infants: A Randomized Clinical
Trial. Journal of Pediatrics 163, 1278-1282. (2013)
•
•
•
•
Compare the effect of 2.5 vs 4 g/kg/d of amino acid
131 infants 500 to 1249 g were randomized
Equal nonprotein energy
Elevated blood urea (BU >70 mg/dL = BU nitrogen
>32.6 mg/dL) occurred in 24% vs 59% (P = .000) and
hyperglycemia (>175 mg/dL) in 34% vs 11% (P = .003)
of the SAA and HAA patients, respectively.
• Body weight, length, and head circumference at 36
weeks and 2 years were similar between groups.
• Bayley Scales of Infant and Toddler Development, Third
Edition score was 94 -¦ 13 in the SAA group and 97 -¦
15 in the HAA group (P = .35)
Burattini I, et al. Targeting 2.5 versus 4 g/kg/day of Amino Acids for
Extremely Low Birth Weight Infants: A Randomized Clinical Trial. The
Journal of Pediatrics 163, 1278-1282. (2013)
Burattini I, et al. Targeting 2.5 vs 4 g/kg/day of Amino Acids for Extremely Low Birth Weight Infants:RCT.
J of Pediatrics 163, 1278-1282. (2013)
Burattini I, et al. Targeting 2.5 vs 4 g/kg/day of Amino Acids for Extremely Low Birth Weight
Infants:RCT. J of Pediatrics 163, 1278-82. (2013)
Burattini I, et al. Targeting 2.5 vs 4 g/kg/day of Amino Acids for Extremely Low Birth Weight Infants:
RCT. J of Pediatrics 163, 1278-1282. (2013)
Blanco CL, Gong AK, Schoolfield J, Green BK, Daniels W, Liechty EA, et al. Impact of
early and high amino acid supplementation on ELBW infants at 2 years. J Pediatr
Gastroenterol Nutr. 2012;54:601-607.
• OBJECTIVE: To examine the effects of early and high intravenous (IV)
amino acid (AA) supplementation on growth, health, and
neurodevelopment of extremely-low-birth-weight (ELBW) infants
throughout their first 2 years of life
• Infants were prospectively randomized in a double-masked fashion and
treated for 7 days with either IV AA starting at:
– 0.5 g/kg/day and increased by 0.5 g/kg every day to 3 g/kg/day
– 2 g/kg/day and advanced by 1 g/kg every day to 4 g/kg/day
• Forty-three of 51 survivors were studied.
– the early and high AA group had a lower MDI at 18 months. This difference
disappeared at 2 years of age
– The early and high AA group z score means for weight, length, and head
circumferences were significantly lower than the standard AA group at most
visits
– Cumulative and single plasma AA concentrations correlated negatively with
MDI and postnatal growth
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Factors that Influence Amino Acid and Acylcarnitine Profiles in
Premature Infants From The Pediatrix-Obstetrix Center for
Research, Education and Quality
• Metabolic profiles were obtained using standard newborn
screening techniques on inborn infants between gestational
ages of 23 - 31 weeks. Metabolic profiles were collected
within the first 24 hours after birth, on approximately day
7, on day 28, and on day 42 of life or at discharge,
whichever came first
• Studied 995 patients; none was subsequently diagnosed
with an inborn error of metabolism.
• Of the 3579 samples, there were 257 (7.2%) amino acid or
acylcarnitine alerts reported in 214 infants (21.4% of infants
studied). Both gestational age and post-birth chronological
age significantly influenced the metabolic profile.
41
Median Amino-Acid Infusion (Zero if not on Fluids)
(grams/kg/day)
Quantiles90
5
4.5
4
3.5
3
2.5
2
1.5
1
0.5
0
23 to 26 weeks
1
7
Quantiles10
27 to 28 weeks
Median
29 to 31 weeks
1
7
Days Since Birth
Factors that Influence Amino Acid and Acylcarnitine Profiles in Premature Infants
From The Pediatrix-Obstetrix Center for Research, Education and Quality
1
7
42
Amino Acids
4
Median Z score
3
2
1
0
Tyr Day=1
Tyr Day=7
Tyr Day=28
Tyr Day=42
Ser Day=1
Ser Day=7
Ser Day=28
Ser Day=42
Gly Day=1
Gly Day=7
Gly Day=28
Gly Day=42
Orn Day=1
Orn Day=7
Orn Day=28
Orn Day=42
Cit Day=1
Cit Day=7
Cit Day=28
Cit Day=42
Glu Day=1
Glu Day=7
Glu Day=28
Glu Day=42
Ala Day=1
Ala Day=7
Ala Day=28
Ala Day=42
Asp Day=1
Asp Day=7
Asp Day=28
Asp Day=42
Val Day=1
Val Day=7
Val Day=28
Val Day=42
Phe Day=1
Phe Day=7
Phe Day=28
Phe Day=42
Met Day=1
Met Day=7
Met Day=28
Met Day=42
His Day=1
His Day=7
His Day=28
His Day=42
Leu-Ile Day=1
Leu-Ile Day=7
Leu-Ile Day=28
Leu-Ile Day=42
-2
Arg Day=1
Arg Day=7
Arg Day=28
Arg Day=42
-1
Essential
To compare the values obtained for each analyte, we calculated a z-score for each patient using the mean and standard deviation values
from a normal term infant population. The z-score for each value was calculated: observed value minus the mean value of a normal term
infant/ divided by the standard deviation from the normal term infant sample. A median z score of greater than 1 or less than -1 means
43
that 50 percent of the patients had a value that was more than 1 standard deviation away from the mean value seen in term infants.
Lipids and Acylcarnitines
44
Median Lipid Infusion (Zero if not on Fluids) (grams/kg/day)
Quantiles90
5
4.5
4
3.5
3
2.5
2
1.5
1
0.5
0
23 to 26 weeks
1
7
Quantiles10
27 to 28 weeks
Median
29 to 31 weeks
1
7
Days Since Birth
Factors that Influence Amino Acid and Acylcarnitine Profiles in Premature Infants
From The Pediatrix-Obstetrix Center for Research, Education and Quality
1
7
45
Acylcarnitines
There was a direct correlation between the dose of intralipids and the
linoleoylcarnitine (C18:2) that was independent of gestational age and age at sample.
5
Median Z score
4
3
2
1
0
-1
-2
C18_2 Day=42
C18_2 Day=28
C18_2 Day=7
C18_2 Day=1
C18_1 Day=42
C18_1 Day=28
C18_1 Day=7
C18_1 Day=1
C18 Day=42
C18 Day=28
C18 Day=7
C18 Day=1
C16_1 Day=42
C16_1 Day=28
C16_1 Day=7
C16_1 Day=1
C16 Day=42
C16 Day=28
C16 Day=7
C16 Day=1
C14_1 Day=42
C14_1 Day=28
C14_1 Day=7
C14_1 Day=1
C14 Day=42
C14 Day=28
C14 Day=7
C14 Day=1
C12_1 Day=42
C12_1 Day=28
C12_1 Day=7
C12_1 Day=1
C12 Day=42
C12 Day=28
C12 Day=7
C12 Day=1
C10_1 Day=42
C10_1 Day=28
C10_1 Day=7
C10_1 Day=1
C10 Day=42
C10 Day=28
C10 Day=7
C10 Day=1
-3
To compare the values obtained for each analyte, we calculated a z-score for each patient using the mean and standard deviation values
from a normal term infant population. The z-score for each value was calculated: observed value minus the mean value of a normal term
infant/ divided by the standard deviation from the normal term infant sample. A median z score of greater than 1 or less than -1 means
46
that 50 percent of the patients had a value that was more than 1 standard deviation away from the mean value seen in term infants.
Vlaardingerbroek et. al. Safety and efficacy of early parenteral lipid and highdose amino acid administration to very low birth weight infants. J Pediatr.
2013 Sep;163(3):638-44.
•
•
•
•
VLBW infants (n = 144; birth weight 862 ± 218 g; gestational age 27.4 ± 2.2 weeks)
were randomized to receive
– 2.4 g of AA/kg/d (control group)
– 2.4 g AA kg/d plus 2-3 g lipids kg/d (AA + lipid group)
– 3.6 g AA kg/d plus 2-3 g lipids kg/d (high AA + lipid group) from birth
onwards.
The nitrogen balance on day 2 was significantly greater in both intervention groups
compared with the control group.
Greater amounts of AA administration did not further improve nitrogen balance
compared with standard AA dose plus lipids and was associated with high
plasma urea concentrations and high rates of urea appearance.
No differences in other biochemical variables, growth, or clinical outcomes were
observed.
47
Note Differences in Slope
First 28 days vs Discharge
48
Nutritional Interactions
• Nutrition is a dynamic interaction between
– what is provided (calories, glucose/carbohydrates,
protein/amino-acids, lipids/fatty-acids/carnitine,
electrolytes, and trace elements)
– how it is provided (intravenous and/or enteral),
– how it is used for energy and growth,
– and how each nutritional component is metabolized
• Just as there are adverse events associated with
drug-drug interactions that relate to metabolism,
the potential for adverse side effects related to
nutritional-nutritional interactions is real
49
Nutritional Interactions
• We believe our data show precisely this type of problem in
the most immature infants (23-26 EGA group).
• Both leucine-isoleucine (primary component of intravenous
amino-acid solutions) and linoleoylcarnitine (linoleic and
linolenic acids are key components of intralipids) are
elevated on day 7 when the doses of amino-acids and
intralipids are highest.
• At the same time,
isovalerylcarnitine+methylbutyrylcarnitine (C5) and
octanoylcarnitine (C8) are elevated.
• The accumulation of these carnitines may lead to the
formation of toxic organic acid metabolites and/or liver
injury.
50
Branched Chain Amino Acids -keto Acids
R
Branched Chain Acyl CoABranched Chain Acyl Carnitine
R
O=CH-COOH
H2N-CH-COOH
R
O=CH-COS-CoA
CH3
Leu
CH2
CH3
R
Ile
CH2
Val
CH
CH
CH3
CH2 CH3
Isovaleryl CoA
Acetyl CoA
(acetoacetate)
Isovaleryl Carnitine
Methylbutryl CoA
Acetyl CoA
Propionyl CoA
Methylbutryl Carnitine
Isobutyrl CoA
Propionyl CoA
Acetyl CoA
Isobutyryl Carnitine
CH3
CH3
COOH
R
CH2
O=CH-COO-CH
CH2
+N(CH )
3
ShortChain
Acyl Carnitine
R’
Medium Chain
Acyl Carnitine
Acetyl-CoA
Acetyl-CoA
Acetyl-CoA
Acetyl-CoA
Acetyl-CoA
Acetyl-CoA
Acetyl-CoA
Acetyl-CoA
Propionyl Carnitine
Acetyl Carnitine
C18:2-CoA
Very Long Chain
Acyl Carnitine
Beta Oxidation
CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH
Linoleic Acid (9,12 octadecadienoic acid, C18:2)
R’-COS-CoA
LinoleylCoA
COOH
CH2
R’COO-CH
CH2
+N(CH )
3
Linoleyl Carnitine
51
Acylcarnitines
Metabolic Byproducts Isovalerylcarnitine+methylbutyrylcarnitine (C5) and
octanoylcarnitine (C8) are elevated
5
Median Z score
4
3
2
1
0
-1
C8 Day=42
C8 Day=28
C8 Day=7
C8 Day=1
C6 Day=42
C6 Day=28
C6 Day=7
C6 Day=1
C5_OH Day=42
C5_OH Day=28
C5_OH Day=7
C5_OH Day=1
C5 Day=42
C5 Day=28
C5 Day=7
C5 Day=1
C4DC Day=42
C4DC Day=28
C4DC Day=7
C4DC Day=1
C4_OH Day=42
C4_OH Day=28
C4_OH Day=7
C4_OH Day=1
C4 Day=42
C4 Day=28
C4 Day=7
C4 Day=1
C3 Day=42
C3 Day=28
C3 Day=7
C3 Day=1
C2 Day=42
C2 Day=28
C2 Day=7
C2 Day=1
FreeCN Day=42
FreeCN Day=28
FreeCN Day=7
FreeCN Day=1
-2
To compare the values obtained for each analyte, we calculated a z-score for each patient using the mean and standard deviation values
from a normal term infant population. The z-score for each value was calculated: observed value minus the mean value of a normal term
infant/ divided by the standard deviation from the normal term infant sample. A median z score of greater than 1 or less than -1 means
52
that 50 percent of the patients had a value that was more than 1 standard deviation away from the mean value seen in term infants.
53
54
55
Carnitine Supplementation?
56
57
Enteral Nutrition
58
Total Enteral Feedings (cc/kg/day)
Note Differences in Enteral Feeding Advancement
Quantiles90
200
180
160
140
120
100
80
60
40
20
0
23 to 26 weeks
1
7
28
Quantiles10
27 to 28 weeks
42
1
7
28 42
Days Since Birth
Median
29 to 31 weeks
1
Factors that Influence Amino Acid and Acylcarnitine Profiles in Premature Infants
From The Pediatrix-Obstetrix Center for Research, Education and Quality
7
28
42
59
Case for Exclusive Use of Human Milk
60
Cristofalo EA, Schanler RJ, Blanco CL, Sullivan S, Trawoeger R, KiechlKohlendorfer U, et al. Randomized trial of exclusive human milk versus
preterm formula diets in extremely premature infants. J Pediatr.
2013;163:1592-1595.
• A multicenter randomized trial in extremely preterm infants
compared a feeding regimen based exclusively on human
milk (donor breast milk with fortifier derived from human
milk) to one using preterm formula and fortifier derived
from cow’s milk
• Infants were eligible if their mothers did not provide their
own breast milk
• Infants fed with the human milk regimen had a shorter
duration of parenteral nutrition and a lower rate of
surgical NEC, but the rate of NEC overall was not
statistically different in the two groups.
• The incidence of NEC in the group fed formula was very
high (21%), much higher than the usual rate of NEC
61
Cristofalo EA et al. J Pediatr. 2013;163:1592-1595.
62
Cristofalo EA, Schanler RJ, Blanco CL, Sullivan S, Trawoeger R, Kiechl-Kohlendorfer U, et
al. Randomized trial of exclusive human milk versus preterm formula diets in
extremely premature infants. J Pediatr. 2013;163:1592-1595.
63
Hair AB, Hawthorne KM, Chetta KE, Abrams SA. Human milk
feeding supports adequate growth in infants </= 1250 grams
birth weight. BMC Res Notes. 2013;6:459.
• Single center, prospective observational cohort study, preterm infants
weighing ≤ 1250 g BW were fed an exclusive human milk-based diet until
34 wks postmenstrual age
• Evaluated 104 infants with mean EGA of 27.6 ± 2.0 wks and BW of 913 ±
181 gm
• Human milk fortification with donor human milk derived fortifier was
started at 60 mL/kg/d and advanced to provide 6 to 8 additional
kilocalories per ounce
• Weight gain was 24.8 ± 5.4 g/kg/day with length 0.99 ± 0.23 cm/week and
head circumference 0.72 ± 0.14 cm/week.
• Weight velocity was affected by day of fortification and day of full feeds
64
Change in Reports of Medical or Surgical NEC in PDX or
VON (Inborn, 401-1500 grams = VLBW All)
PDX ALL Inborn
VON all US Inborn
Q1
2010
2011
Q2
10.0%
9.0%
8.0%
7.0%
6.0%
5.0%
4.0%
3.0%
2.0%
1.0%
0.0%
2008
2009
2012
Vohr BR, et al. Persistent beneficial effects of breast milk ingested in the
neonatal intensive care unit on outcomes of extremely low birth weight
infants at 30 months of age. Pediatrics 2007;120(4):e953-e959.
• For every 10 mL/kg per day increase in breast milk
– Mental Developmental Index increased by 0.59
points,
– Psychomotor Developmental Index by 0.56 points,
– Behavior percentile score by 0.99 points
– Risk of rehospitalization between discharge and
30 months decreased by 5%.
66
Mean MDI and PDI scores at 18 and 30 months according to any BM feeding.
Vohr B R et al. Pediatrics 2007;120:e953-e959
67
©2007 by American Academy of Pediatrics
Morgan J, Young L, McGuire W. Slow advancement of enteral feed volumes to
prevent necrotizing enterocolitis in very low birth weight infants. Cochrane
Database Syst Rev. 2013 Mar 28;3:CD001241.
• Five randomized controlled trials in which a total of 588
infants participated. Few participants were extremely
preterm, extremely low birth weight or growth restricted.
• The trials defined slow advancement as daily increments of 15
to 20 ml/kg and faster advancement as 30 to 35 ml/kg.
• Meta-analyses did not detect statistically significant effects on
the risk of necrotizing enterocolitis (typical risk ratio (RR) 0.97,
95% confidence interval (CI) 0.54 to 1.74) or all-cause
mortality (RR 1.41, 95% CI 0.81 to 2.74).
• Infants who had slow advancement took significantly longer
to regain birth weight (reported median differences two to six
days) and to establish full enteral feeding (two to five days).
68
Alfaleh K, Bassler D. Probiotics for prevention of necrotizing
enterocolitis in preterm infants (updated 2013). Cochrane Database
Syst Rev. In press.
• 24 trials
• Decrease in necrotizing enterocolitis (NEC)
– Relative risk [RR]= 0.43, 0.33-0.56;
– Risk difference [RD] = −0.03, 95% -0.04 to −0.02
• Decrease in all-cause mortality
– RR = 0.65, 0.52-0.81;
– RD −0.01, 95% CI −0.02 to −0.00, P = .01
• Length of stay was 3-4 days shorter.
• There was no probiotic-related sepsis in the clinical trials,
although this is rarely reported outside trials
Extra Slides
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Bloom et al. Improving Growth of Very Low Birth
Weight Infants in the First 28 Days
Pediatrics 2003;112;8-14
Bloom et al. Pediatrics 2003:112:8-14
71
The intestinal microbiome, probiotics
and prebiotics in neurogastroenterology.
Gut Microbes 4:1, 17–27; January/February 2013
72
73
Table 6. Current Daily Parenteral Recommendations for Infants and Children 38 .
Vanek V W et al. Nutr Clin Pract 2012;27:440-491
Copyright © by The American Society for Parenteral and Enteral Nutrition
Table 7. Current Parenteral and Enteral Vitamin and Trace Element Recommendations for
Preterm and Term Neonates.
Vanek V W et al. Nutr Clin Pract 2012;27:440-491
Copyright © by The American Society for Parenteral and Enteral Nutrition