3. Introduction
Proper nutrition in infancy is essential for
– normal growth
– immunity to infection
– optimal neurologic and cognitive development.
Providing adequate nutrition to preterm infants is
challenging because of several problems, some of them
unique to these small infants. These problems include:
– immaturity of bowel function
– inability to suck and swallow
– high risk of necrotizing enterocolitis (NEC)
– illnesses that may interfere with adequate enteral
feeding (e.g. RDS, patent ductus arteriosus)
– medical interventions that preclude feeding (e.g.,
umbilical vessel catheters, exchange transfusion,
indomethacin therapy)
4. Long term outcome and Barker’s
Hypothesis
There is evidence that adaptations in the metabolic and hormonal
milieu in the fetal and immediate neonatal period can result in
immediate benefit but adverse long-term outcome.
Nutritional insults at a vulnerable period of brain development, for
example, have been shown to be associated with effects on brain
size, cell number, behavior and learning memory.
The emergence of cardiovascular disease, hypertension, insulin
resistance and obesity in low birth weight infants is another concern
raising the issue of long-term ‘‘programming.’’
In addition, there may be transgenerational effects as evidenced by
the association of low maternal birth weight and higher offspring
hypertension in adulthood.
These changes may be exacerbated by postnatal malnutrition and
poor growth that preterm infants experience.
5. PHYSIOLOGY AND
PATHOPHYSIOLOGY
The gut has formed and has completed its rotation back
into the abdominal cavity by 10 weeks of gestation.
By 16 weeks, the fetus can swallow amniotic fluid.
GI motor activity is present before 24 weeks, but
organized peristalsis is not established until 29-30
weeks and is facilitated by antenatal corticosteroid
treatment.
Coordinated sucking and swallowing develops at 32-34
weeks.
By term, the fetus swallows about 150 cc/kg/day of
amniotic fluid, which has 275 mOsm/L, contains
carbohydrates, protein, fat, electrolytes,
immunoglobulins and growth factors, and plays an
important role in development of GI function. Preterm
birth interrupts this development.
6. Importance of Enteral Feeding
Even if nutrients are provided parenterally, lack of
enteric intake leads to
– decreased circulating gut peptides
– slower enterocyte turnover and nutrient transport
– decreased bile acid secretion
– increased susceptibility to infection due to impaired barrier
function by intestinal epithelium, lack of colonization by normal
commensal flora and colonization by pathogenic organisms.
For fat digestion, the newborn depends on lingual lipase,
which is stimulated by sucking and swallowing and by
nutrients in the stomach but not the small bowel.
9. Trophic feedings for parenterally fed
infants (Review)
2008 The Cochrane Collaboration
Trophic feeding defined as dilute or full strength feedings providing < = 25 ml/kg/d
for > = 5d (5-10days)
Trophic feedings vs. no feedings (10 trials): Among infants given trophic
feedings, there was an overall reduction in days to full feeding (weighted mean
difference [WMD] = -2.6 [95% confidence limits = -4.1, -1.0]), total days that
feedings were held (WMD = -3.1 [-4.6, -1.6]), and total hospital stay (WMD = -11.4
[-17.2, -5.7] compared to infants given no enteral nutrient intake.
Tests for heterogeneity were significant in analyses of days to full enteral feedings,
days to regain birth weight, days of phototherapy, and hospital stay.
There was no significant difference in necrotizing enterocolitis, although the findings
do not exclude an important effect (relative risk = 1.16 [0.75, 1.79]; risk difference =
0.02 [-0.03, 0.06].
Trophic feedings vs. advancing feedings (one trial): Infants given trophic
feedings required more days to reach full enteral feeding (13.4 [8.2, 18.6]) and
tended to have a longer hospital stay (11.0 [-1.4, 23.4]) than did infants given
advancing feedings. With only eight total cases of necrotizing enterocolitis, trophic
feedings were associated with a marginally significant reduction in necrotizing
enterocolitis (relative risk =0.14 [0.02, 1.07]; risk difference = -0.09 [-0.16, -0.01].
10. Authors’ conclusions
In both comparisons, the group with the greater enteral intake (trophic feedings in
the first comparison and advancing feedings in the second comparison) required
significantly less time to reach full feedings and had a significant or near significant
reduction in hospital stay.
In both comparisons, the group with the greater intake also had a higher incidence of
NEC although the difference was not statistically significant. The concern is greatest
for the advancing feeding regimen. Even when trophic feedings were compared to no
feedings, the relative risk for NEC was 1.16 (0.75 - 1.79), a finding consistent with a
16% increase in NEC and a NNH of 50. A true increase of this magnitude might
outweigh any shorter or long-term benefits of trophic feedings. Moreover, the 95% CI
does not exclude the possibility that trophic feedings increase NEC by as much as
79% with a NNH of 17.
Whether no feedings, trophic feedings, or advancing feedings should initially be used
is difficult to discern for a variety of reasons—the inherent difficulty of assessing
enteral feedings in high-risk infants, the limited sample size and methodologic
limitations of most studies to date, unexplained heterogeneity with respect to a
number of outcomes, the potential for bias to affect the findings in unblinded studies,
and the large number of infants who must be studied to assess the effect on
necrotizing enterocolitis.
One or more large, well designed, multi-center trials are needed to compare these
approaches to early feeding with respect to important clinical outcomes. A conclusive
evaluation would assess effects on not only the survival rate without necrotizing
enterocolitis prior to discharge from the neonatal unit but also on the survival rate
without severe gastrointestinal or neurodevelopmental disability at >= 18 months
age.
11. Nasal versus oral route for placing feeding tubes in
preterm or low birth weight infants. 2008 Cochrane
Collaboration
Main results
Two small randomised trials were identified.
Only one trial reported data on the pre-specified primary outcomes
for this review. This trial found no evidence of effect on the time
taken to establish enteral feeding nor the time taken to regain birth
weight. However, the trial was underpowered (N= 46) to exclude
modest effect sizes.
Authors’ conclusions
There are insufficient data available to inform practice. A large
randomised controlled trial is required to determine if the use of
naso vs oro-enteric feeding tubes affects feeding, growth and
development, and the incidence of adverse consequences in
preterm or low birth weight infants.
12. Continuous nasogastric milk feeding versus
intermittent bolus milk feeding for
premature infants less than 1500 grams,
2008 Cochrane collaboration
Main results
Overall, the seven included trials, involving 511 infants, found no
differences in time to achieve full enteral feeds between feeding methods
(weighted mean difference (WMD 2 days; 95%CI -0.3, 3.9) .
In the subgroup analysis of those studies comparing continuous nasogastric
vs. intermittent bolus nasogastric milk feedings the findings remained
unchanged (WMD 2 days, 95% CI -0.4, 4.1).
There was no significant difference in somatic growth and incidence of NEC
between feeding methods irrespective of tube placement.
One study noted a trend toward more apneas during the study period in
infants fed by the continuous tube feeding method compared to those fed
by intermittent feedings delivered predominantly by orogastric tube
placements [mean difference (MD) 14.0 apneas during study period; 95%
CI -0.2, 28.2].
In subgroup analysis based on weight groups, one study suggested that
infants less than 1000 grams and 1000 - 1250 grams birth weight gained
weight faster when fed by the continuous nasogastric tube feeding method
compared to intermittent nasogastric tube feeding method (MD 2.0 g/day;
95% CI 0.5, 3.5; MD 2.0 g/day; 95% CI 0.2, 3.8, respectively).
13. A trend toward earlier discharge for infants less than 1000 grams birth
weight fed by the continuous tube feeding method compared to
intermittent nasogastric tube feeding method (MD -11 days; 95% CI -21.8,
-0.2).
Authors’ conclusions
Small sample sizes, methodologic limitations, inconsistencies in controlling
variables that may affect outcomes, and conflicting results of the studies to
date make it difficult to make universal recommendations regarding the
best tube feeding method for premature infants less than 1500 grams.
The clinical benefits and risks of continuous vs. intermittent nasogastric
tube milk feeding cannot be reliably discerned from the limited information
available from randomized trials to date.
14. Transpyloric versus gastric tube feeding for preterm
infants. 2008 Cochrane Collaboration
Data from nine trials were available.
No evidence of an effect on short term growth rates was found:
weight:WMD -0.7 g/week (95% confidence interval (CI) -25.2, 23.8); crown
heel length: WMD -0.7 mm/week (95% CI -2.4, 1.0); head circumference:
WMD 0.6 mm/week (95% CI -0.9, 2.1).
Longer term growth was reported in one study. There were not any
statistically significant differences between the groups in the mean body
weight or occipitofrontal head circumference at three months or at six
months corrected age.
None of the included studies provided data on neurodevelopmental
outcomes.
Transpyloric feeding was associated with a greater incidence of gastro-
intestinal disturbance (RR 1.45, 95% CI 1.05, 2.09). There was some
evidence that feeding via the transpyloric route increased mortality (RR
2.46, 95% CI 1.36, 4.46). However, the outcomes of the study that
contributed most to this finding were likely to have been affected by
selective allocation of the less mature and sicker infants to transpyloric
feeding.
15. No statistically significant differences in the incidence of other adverse
events, including necrotising enterocolitis, intestinal perforation, and
aspiration pneumonia was found.
Authors’ conclusions
No evidence of any beneficial effect of transpyloric feeding in preterm
infants was found. However, evidence of adverse effects was noted.
Feeding via the transpyloric route cannot be recommended for preterm
infants
16. Ad libitum or demand/semi-demand feeding versus
scheduled interval feeding for preterm infants,
2008 Cochrane collaboration
Seven randomised controlled trials that compared ad libitum or demand/semi-
demand regimes with scheduled interval regimes in preterm infants in the transition
phase from intragastric tube to oral feeding were found.
The trials were generally small and of variable methodological quality. The duration of
the intervention and the duration of data collection and follow up in most of the trials
is not likely to have allowed detection of measurable effects on growth.
The single trial that assessed growth for longer than one week found that the rate of
weight gain was lower in the ad libitum fed infants [mean difference -3.30 (95%
confidence interval -6.2 to -0.4) grams per kilogram per day].
Two trials reported that feeding preterm infants using an ad libitum or demand/semi-
demand feeding regime allowed earlier discharge from hospital, but the other trials
did not confirm this finding.
Not able to undertake meta-analyses because of differences in study design and in
the way the findings were reported.
Authors’ conclusions
There are insufficient data at present to guide clinical practice. A large randomised
controlled trial is needed to determine if ad libitum of demand/semi-demand feeding
of preterm infants affects clinically important outcomes. This trial should focus on
infants in the transition phase from intragastric tube to oral feeding and should be of
sufficient duration to assess effects on growth and time to oral feeding and hospital
discharge.
20. Formula milk versus maternal breast milk for
feeding preterm or low birth weight infants
2008 Cochrane Collaboration.
Main results
No eligible trials were identified.
Authors’ conclusions
There are no data from randomised trials of formula milk versus
maternal breast milk for feeding preterm or low birth weight infants.
This may relate to a perceived difficulty of allocating an alternative
feed to an infant whose mother wishes to feed with her own breast
milk.
Maternal breast milk remains the default choice of enteral nutrition
because observational studies, and meta-analyses of trials
comparing feeding with formula milk versus donor breast milk,
suggest that feeding with breastmilk has major non-nutrient
advantages for preterm or low birth weight infants.
21.
22. Donor breast milk versus infant formula for preterm
infants: systematic review and meta-analysis
Cochrane collaboration 2006
Results:
•Seven studies (including five randomised controlled trials), all from the 1970s
and 1980s, fulfilled the inclusion criteria. All studies compared the effect of sole
donor breast milk with formula (combined n = 471). One of these also compared
the effect of donor breast milk with formula given as a supplement to mother’s
own milk (n = 343). No studies examined fortified donor breast milk.
•A meta-analysis based on three studies found a lower risk of NEC in infants
receiving donor breast milk compared with formula (combined RR 0.21, 95% CI
0.06 to 0.76).
•Donor breast milk was associated with slower growth in the early postnatal
period, but its long-term effect is unclear.
Conclusion:
•Donor breast milk is associated with a lower risk of NEC and slower growth in
the early postnatal period, but the quality of the evidence is limited. Further
research is needed to confirm these findings and measure the effect of fortified
or supplemented donor breast milk.
23. Protein supplementation of human milk for
promoting growth in preterm infants
Cochrane collaboration 2000
MAIN RESULTS:
•Protein supplementation of human milk results in increases in short term
weight gain (WMD 3.6 g/kg/day, 95% CI 2.4 to 4.8 g/kg/day), linear growth
(WMD 0.28 cm/week, 95% CI 0.18 to 0.38 cm/week) and head growth (WMD
0.15 cm/week, 95% CI 0.06 to 0.23 cm/week).
•There are insufficient data to evaluate long term neurodevelopmental and
growth outcomes. There are too few infants studied to be certain that adverse
effects of protein supplementation are not increased. Blood urea levels are
increased (WMD 1.0 mmol/l, 95% CI 0.8 to 1.2 mmol/l).
REVIEWER'S CONCLUSIONS:
•Protein supplementation of human milk in relatively well preterm infants results
in increases in short term weight gain, linear and head growth. Urea levels are
increased, which may reflect adequate rather than excessive dietary protein
intake.
•Further research should be directed towards the evaluation of specific levels
of protein intake in preterm infants and the clinical effects of supplementation
with protein, including long term growth and neurodevelopmental outcomes.
This may best be done in the context of refinement of available multicomponent
fortifier preparations.
24. Multicomponent fortified human milk for promoting growth in
preterm infants.
Cochrane collaboration 2004
MAIN RESULTS
• Supplementation of human milk with multicomponent fortifiers (in the form of protein,
calcium, phosphate, and carbohydrate, as well as vitamins and trace minerals) is
associated with short term increases in weight gain, linear and head growth. There is no
effect on serum alkaline phosphatase levels; it is not clear if there is an effect on bone
mineral content. Nitrogen retention and blood urea levels appear to be increased.
•There are insufficient data to evaluate long term neurodevelopmental and growth
outcomes, although there appears to be no effect on growth beyond one year of life.
•Use of multicomponent fortifiers does not appear to be associated with adverse effects,
although the total number of infants studied and the large amount of missing data
reduces confidence in this conclusion. Blood urea levels are increased and blood pH
levels minimally decreased, but the clinical significance of this is uncertain.
REVIEWER'S CONCLUSIONS:
•Multicomponent fortification of human milk is associated with short-term improvements in
weight gain, linear and head growth. Despite the absence of evidence of long-term
benefit and insufficient evidence to be reassured that there are no deleterious effects, it is
unlikely that further studies evaluating fortification of human milk versus no
supplementation will be performed.
•Further research should be directed toward comparisons between different proprietary
preparations and evaluating both short-term and long-term outcomes in search of the
"optimal" composition of fortifiers.
25. Fortification of Preterm Human Milk for Feeding
Preterm Infants – Yale Pediatric Protocol
Preterm human milk (PTHM) is milk expressed by a mother for her infant following a preterm
delivery.
– may be stored in the Breast Milk Refrigerator for up to 48 hours.
– If the milk will not be fed to the infant within that time, it should be frozen as early as possible after
expression in appropriate-sized volumes and then gently thawed prior to use. Once thawed, it should be
used within about 4 hours.
Infants should be fed full strength human milk as their initial enteral feeding.
When to fortify:
– After an infant tolerates full enteral feeding of full-strength human milk for 5-7 days
– Or, after he/she tolerates about 75% his/her total daily volume (IV + NG) as full strength human milk
How to fortify
– adding a powdered Human Milk Fortifier
– by mixing human milk with an equal volume of Premature Formula
Mixing equal volumes of human milk and Premature Formula or Natural Care results in a nutrient concentration that equals
an average between human milk and formula
– Or, by mixing human milk with an equal volume of Natural Care(similac) Human Milk Fortifier.
The decision on which method of fortification to use will depend upon the mother's milk
production with discussion with Lactation Consultant.
Why fortify
– Increases the content of nutrients in the infant's diet, esp calcium and phosphorus. (See table next page)
– The composition of PTHM varies with the duration of lactation; an approximate composition of "mature"
PTHM is also shown
26.
27.
28. Special Formula Use
Recommendations
Nutrition Practice Care Guidelines for Preterm Infants In the Community. Revised August 2006.
Developed by Child Development and Rehabilitation Center, Nutrition Services, Oregon Department of Human Services, Nutrition & Health
Screening – WIC Program. Oregon Pediatric Nutrition Practice Group
Preterm formula and Human Milk Fortifier: generally for infants
weighing less than 1,850 to 2,000 gm (about 4 to 4 ½ lbs). It is
inappropriate for most infants who weigh more than 2.5 kg (5 ½ lbs) or are
taking in over 500 ml daily to be fed premature formulas (Enfamil
Premature Lipil or Similac Special Care) or Human Milk Fortifiers (Similac
HMF, Similac Natural Care or Enfamil HMF) for all their feeds because of the
higher vitamin A and vitamin D content of these formulas and the possible
risk of hypervitaminosis.
Transitional Formulas: (also called “post-discharge premature formulas”)
Formulas such as Enfamil EnfaCare Lipil and Similac Neosure Advance
provide 22 kcal/oz and have higher levels of protein, calcium, phosphorus,
vitamins and other minerals than standard infant formulas. Research has
shown that premature infants fed these formulas have improved growth
and bone mineralization compared to those fed standard infant formulas.
*See recommendation below for length of time an infant needs to remain on a
transitional formula.
29. Specialized formulas
– These include Pregestimil, Alimentum, Nutramigen, Neocate and
Elecare, and may be indicated based on feeding intolerance.
– Enfamil AR is not indicated for preterm infants due to the risk of the
formation of lactobezoars (hard clumps of undigested milk curds).
These are “term” formulas and thus have less calcium, phosphorus, and
protein than transitional formulas. If preterm infants are given these
formulas, they should be followed more closely by an RD and the
appropriate labs should be checked.
Soy-based formulas are not recommended for preterm infants. Preterm
infants receiving soy formula have suboptimal carbohydrate and mineral
absorption and utilization than cow’s milk-based formula. AAP doesn’t
recommend soy formula for infants born < 1800 g since preterm infants
showed significantly less weight gain, less linear growth, and lower serum
albumin levels than those infants receiving cow’s milk-based formulas.
Studies also have shown lower levels of bone marker formation in the
premature population which can lead to osteopenia.
Goat’s milk is not recommended for preterm infants. Goat’s milk is
deficient in folic acid and vitamin B6. It is also higher in protein than human
milk and infant formula which puts the premature infant at risk for
dehydration due to the higher renal solute load.
30. Dorset County Hospital Neonatal Unit
Guidelines for enteral feeding (Mar05)
Milk of choice, in order of preference, is:
– 1. Breast milk – suckled by baby from the breast
– 2. Mother’s expressed breast milk (EBM), fresh
– 3. Mother’s EBM, frozen
– 4. Donor EBM*
– 5. Formula feed appropriate to gestational age and birth weight
* consider using when:
baby deemed at high risk of developing necrotising
enterocolitis (NEC) – see section 3
if it is available, to intensive care babies
poor tolerance of formula feeds
NB parental consent should be sought prior to a baby being given
donor EBM
This hospital actively promotes the benefits of breast feeding for all
infants. There are particular benefits of breast milk for the preterm
infant and sick neonate (eg reduced incidence of necrotising
enterocolitis - ref 1).
31. Dorset County (cont’d)
Early nutrition in the preterm group
All mothers should be encouraged to produce milk for their baby as soon
as possible after delivery if their baby is not able to feed naturally. Even if
the mother is not planning to breast feed in the longer term or unwilling to
breast feed, they should be advised why EBM is the best nutritional support
for their baby.
For premature infants whose mother’s wish to breast feed in the longer
term, skin to skin contact should be strongly encouraged from an early
stage. Cup feeding is often possible from 30 weeks gestation. Bottle feeding
should be avoided if at all possible given the different technique a baby
uses to bottle feed compared to feeding at the breast.
If formula feeds are being used, the baby should not be started on a
preterm formula until they are tolerating 150 ml/kg/day of a standard
formula feed.
32. Dorset County (cont’d)
Early nutrition in the preterm group
a) Under 2kg
For babies with a birth weight of less than 1.2 kg (and occasionally larger
babies) parenteral nutrition will normally be necessary during the first 1-2
weeks of life. This should be written up as soon as possible after delivery
so that it can be commenced within 1-2 days of delivery (see TPN
guidelines).
i) Non-nutritive feeding (minimal enteral nutrition):
– Small amounts of breast milk started in the first few days of life (day 1 if
possible)
– encourage gut maturity (ref 2)
– Start at 1ml every 4-6 hours if <1kg (ref 5) and 1ml/hr if >1kg (ref 3). Maternal
EBM is preferable to donor breast milk.
– Please note section on management of infants at high risk of NEC
(section 3)
ii) Rate of increase of feed:
– Once tolerating minimal enteral nutrition, increase the volume given at each
feed. The rate of increase should be decided for each individual baby but would
normally be less than 35ml/kg per 24 hours for babies less than 1200gm (ref 4).
Larger babies will possibly tolerate faster increments in feed volume.
33. Dorset County (cont’d)
Early nutrition in the preterm group
iii) Final feed volume:
– Increase feed volumes up to a maximum of:
– 200-220 ml/kg/day for EBM
– 180 ml/kg for term formula (or Nutriprem 2)
– 160 ml/kg/day for preterm formula*
Once an infant is tolerating >50% of their total fluid volume enterally, lipid
can be discontinued in the TPN (see TPN guidelines).
* If formula feeds are being used, the baby should not be started on a
preterm formula until they are tolerating 150 ml/kg/day of a standard
formula feed.
b) greater than 2kg
Where possible allow to demand feed.
For well infants below 37 weeks gestation, consider starting feeds at
60ml/kg/day on day 1 of feeding aiming to reach 150ml/kg/day within 4
days depending on progress.
34. Dorset County (cont’d)
Early nutrition in the preterm group
3. High risk groups for NEC
Particular high risk groups include:
– Preterm infants < 1kg
– Severe intrauterine growth retardation
– Absent/reversed end diastolic flow on umbilical artery Doppler
– Sepsis
For infants with absent or reversed end diastolic flow do not feed enterally
for 3 days.
For at risk groups consider waiting for maternal EBM before starting feeds.
In these circumstances feeding human milk at a rate 1 ml every 4-6 hours
is recommended (ref 5). If maternal EBM is not available for these groups
consider the use of donor EBM.
For babies at high risk of necrotising enterocolitis (NEC) there is some
evidence that a rate of increase not exceeding 20ml/kg per 24 hours
reduces the incidence of NEC (ref 6).
* After a suspected episode of NEC feeds should be reintroduced using EBM
(maternal if possible but donor if not available). If maternal EBM not
available and mother refused permission to use donor EBM, consider using
Pregestimil (see section 9 for advise on increasing calorie intake if
inadequate growth on this formula).
35. References:
1. Lucas A, Cole TJ. Breast milk and neonatal necrotising enterocolitis.
Lancet 1990; 336: 1519-1523.
2. McClure RJ and Newell SJ. Randomised controlled trial of trophic
feedingand gut motility. Arch Dis Child Neonatal Ed 1999; 80: F54-58.
3. Child Nutrition Panel “Feeding the preterm infant”. Z740127 May 2002
4. Kennedy KA et al. Rapid versus slow rate of advancement of feeding in
parenterally fed low birth weight infants. Cochrane Review. 2001.
5. King C. Neonatal Unit Enteral Feeding Policy. Hammersmith Hospital NHS
Trust 2000.
6. Anderson DM and Kliegman RM. The relationship of neonatal
alimentation practice to the occurrence of endemic necrotising enterocolitis.
Am J Perinatol 1991; 8: 62-67.
7. Cooke RJ and Embleton ND. Feeding issues in preterm infants. J. Pediat.
Neonatal Ed 2000; 83: F215-218.
8. Nutrition in low birth weight infants. Clinical Paediatric Dietetics 2001.
37. GROUP 1. 34-36 weeks gestational age and birthweight > 1.5Kg who is on the
neonatal unit due to a lack of transitional care capacity.
Timing of enteral: Immediately
Mode of enteral: NG or oral
Type of milk: EBM or Nutriprem (as per policy)
Rate of increase: Full feeds as soon as able
GROUP 2. 34-36 weeks gestational age and birthweight > 1.5Kg admitted to
Neonatal Unit for whatever reason
Feeding will depend on primary pathology. If considered ready for feeding, then feed
as Feeding Group 1.
GROUP 3. 34-36 weeks gestational age and birthweight < 1.5Kg
These infants are under the 2nd centile.
Timing of enteral: Delay for up to 24 hours in marked IUGR, or make decision to feed
immediately
Mode of enteral: NG or oral
Type of milk: EBM or Nutriprem 1 (as per policy)
Rate of increase: 60mls/kg increasing at a maximum of 1ml/Kg per day
(0.5ml 12 hourly) up to total of 150/ml/kg/day
GROUP 4. 31-33 weeks, NO IUGR or A/REDF on antenatal Doppler
Timing of enteral: Immediately
Mode of enteral: NG
Type of milk: EBM or Nutriprem 1(as per policy)
Rate of increase: 60mls/kg, max increase per day < 25ml/kg
(0.5ml/h, 8 hourly) as tolerated*
38. GROUP 5. <= 30 weeks, No IUGR (> 2nd centile) or A/REDF on antenatal
Doppler
Timing of enteral: Delay for 24 hours after birth
Mode of enteral: NG
Type of milk: EBM or Nutriprem 1(as per policy)
Rate of increase: 1ml/kg, increasing maximum 8 hourly as tolerated* for first 72
hours. Increase to 0.5ml/kg 6 hourly maximum as tolerated* after 72 hours of age.
Note: Slow feeding to 12 hourly if evidence of failure to tolerate*.
Maximum daily increase not to exceed 25 mls/kg per day.
GROUP 6. <= 33 weeks, IUGR (<= 2nd centile) or A/REDF on antenatal
Doppler
Timing of enteral: Delay at least 24 hours
Mode of enteral: NG
Type of Milk: EBM or Donor EBM (see below)
Rate of increase:
– <= 1kg: 0.5ml/hr initially increasing by 0.5 ml/24 hours as tolerated
– > 1kg 1ml/hr initially increasing by 1ml/24 hours as tolerated
When full feeds established continue, if using Donor EBM, continue on full feeds
(maximum 165ml/Kg per day) for at least 5 days. Switch to Nutriprem 1 after this
time.
Parenteral Nutrition (PN) will be required for this group (see PN protocol)
*Tolerating enteral feeds
Babies are considered to be tolerating enteral feeds if
• 4 hourly NG aspirates are < 25% of total infused in the preceding 4 hours
• No significant abdominal distension
• No significant vomiting
• No bile-stained aspirates
41. Longchain polyunsaturated fatty acid supplementation in preterm infants
Cochrane collaboration 2003
Main results
•Of the eleven randomised trials included in the review, two of these were not
classified as of high quality despite blinded assessment and complete follow-up, due to
problems with assessment methodology.
Visual acuity
Visual acuity over the first year was measured by Teller acuity cards in six studies, by
VEP in four studies and by ERG in two studies. Most studies found no significant
differences in any visual assessment between supplemented and control infants.
Development
Most of the trials have used Bayley Scales of Infant Development (BSID) at 12 to 24
months postterm and shown no significant effect following supplementation. Meta-
analysis of BSID of three studies (Fewtrell 2002, O'Connor 2001, van Wezel 2002)
shows no significant effect of supplementation on development. Carlson 1993 and
Carlson 1996 demonstrated lower novelty preferences (possibly predictive of lower
intelligence) in the supplemented compared with the control group. The investigators
however concluded that supplemented infants may have more rapid visual information
processing given that they had more looks and each look was of shorter duration.
42. Growth
Most trials have reported no significant effect of LCPUFA supplementation on growth
of preterm infants. Two trials (Carlson 1993, Carlson 1996) suggest that LCPUFA
supplemented infants grow less well than controls, possibly due to a reduction in AA
levels which occurs when n-3 supplements are used without n-6 supplements. Recent
trials with addition of AA to the supplement have reported no significant effect on
growth. Fewtrell 2002 reported mild reductions in length and weight z scores at 18
months.
Contrary to these results, the meta-analysis of five studies (Uauy 1992, Carlson 1996,
Hansen 1997, Vanderhoof 1999, Innis 2002) showed increased weight and length at
two months post-term in supplemented infants.
Side effects
Uauy 1992 reported no significant effect of LCPUFA supplementation on bleeding time
and red cell membrane fragility.
Reviewers' conclusions
Infants enrolled in the trials were relatively mature and healthy preterm infants.
Assessment schedule and methodology, dose and source of supplementation and fatty
acid composition of the control formula varied between trials. No long-term benefits
were demonstrated for infants receiving formula supplemented with LCPUFA. There
was no evidence that supplementation of formula with n-3 and n-6 LCPUFA impaired
the growth of preterm infants.
43. Is supplementary iron useful when preterm infants
are treated with erythropoietin? BestBets 2006
In [a preterm infant who is receiving rHuEPO therapy] does [iron supplementation]
reduce the requirement for [blood transfusion]? If so, what method of administration
and dose reduces it most successfully
44. Comment(s)
•Anaemia in premature infants is a common problem. Although erythropoietin is
not used widely in neonatal practice, there is evidence of its efficacy in reducing
the need for transfusion in preterm infants,(Shannon) especially if they are not
extremely small or sick.(Soubasi). It is regularly used in situations where blood
transfusion is unacceptable.
•Iron supplementation has been a standard in neonatal care for preterm infants
for many years and helps to reduce late anaemia (Franz) if given with vitamins,
especially vitamin E.(Jansson). However, when stimulating erythropoiesis with
rHuEpo to reduce the need for transfusion, iron availability becomes critical.
• Several studies have investigated rHuEpo efficacy in preterm infants and most
of them have used supplementary iron in either the oral or parenteral routes. The
literature on the use of rHuEpo and iron mostly consists of studies on dose
variation of rHuEpo rather than variation in the iron supplementation.
•Our search yielded seven studies, but one(Pollak) was excluded owing to poor
methodological quality. Two studies by Carnielli et al and Fujiu et al compared
rHuEpo and oral iron supplementation with rHuEpo alone; however, the
interpretation of the data is difficult because Carnielli et al reported their results
only as mean values and logarithms, making statistical analysis difficult. Fujiu et
al found that no infants in either arm of their study required a blood transfusion.
45. •Although this may suggest that there was no difference between the groups, the
sample size was small, with only 24 infants in total, and the clinical equivalence could
not be shown. In addition, the authors state that losses due to phlebotomy in their
study were lower than those in other similar studies. This may be relevant, as one of
the most common causes of the anaemia of prematurity is iatrogenic blood loss.
•Kivivuori et al and Meyer et al compared rHuEPO treatment and parenteral iron
supplementation with rHuEPO treatment and oral iron supplementation. Combined
data from the two studies showed that there was no significant difference between the
groups for the number of blood transfusions given (odds ratio (OR) 1.65, 95%
confidence interval (CI) 0.41 to 6.64). This seems to suggest that oral iron
supplementation is at least sufficient. However, one study used intravenous iron
supplementation whereas the other used intramuscular iron supplementation.
Differences in absorption of these two different routes may be relevant, but no study
has been carried out comparing intravenous with intramuscular iron supplementation.
•Bader et al and Nazir et al compared infants receiving rHuEPO treatment and high-
dose oral iron supplementation with those receiving rHuEPO treatment and low-dose
oral iron supplementation. There was no significant difference between the two groups,
when combining data for the two studies, regarding the number of blood transfusions
(OR 0.46, 95% CI 0.04 to 5.75).
46. Preterm infants on special-care baby units frequently become anaemic and require
top-up blood transfusions. Preterm infants often have low iron stores; this becomes
more evident if they do not receive transfusions or iron supplementation.
Erythropoietin is used occasionally to stimulate red cell production and prevent
anaemia, and the increased erythropoiesis that occurs as a result of rHuEPO
treatment will deplete iron stores.
The studies currently available do not give an adequate answer to the question as to
which is the best mode and dose of iron supplementation with rHuEpo treatment. On
the basis of the principle of using the lowest effective dose and the least invasive
mode of administration, at present, low-dose oral iron would seem appropriate for
supplementation when rHuEpo is used in preterm infants.
Clinical Bottom Line
Evidence available to strongly support any specific recommendation for iron
supplementation with recombinant erythropoietin treatment in premature infants
(grade D) is insufficient. Low-dose oral iron supplementation is not inferior to other
treatment regimens (grade B).
47. Glutamine supplementation to prevent morbidity
and mortality in preterm infants
Cochrane collaboration 2008
Main results
•2365 preterm infants have participated in seven randomised controlled trials. All of
the participating infants were of very low birth weight.
•Three trials assessed enteral glutamine supplementation and four trials assessed
parenteral glutamine supplementation.
•The trials were generally of good methodological quality with adequate allocation
concealment, blinding of caregivers and assessors to the intervention, and complete
or near-complete follow-up of recruited infants.
•Glutamine supplementation does not have a statistically significant effect on
mortality: typical relative risk 0.98 (95% confidence interval 0.80 to 1.20); typical risk
difference 0.00 (95% confidence interval -0.03 to 0.02).
•The only trial that assessed long-term outcomes did not find any statistically
significant differences in various assessments of neurodevelopment at 18 months
corrected age. Glutamine supplementation does not have a statistically significant
effect on other neonatal morbidities including invasive infection, necrotising
enterocolitis, time to achieve full enteral nutrition, or duration of hospital stay.
Authors' conclusions
•The available data from good quality randomised controlled trials indicate that
glutamine supplementation does not confer benefits for preterm infants. The narrow
confidence intervals for the effect size estimates suggest that a further trial of this
intervention is not a research priority.
52. Probiotics for prevention of necrotizing
enterocolitis in preterm infants
Cochrane review 2007
Main results
Nine eligible trials randomizing 1425 infants were included.
Included trials were highly variable with regard to enrollment criteria (i.e. birth weight
and gestational age), baseline risk of NEC in the control groups, timing, dose,
formulation of the probiotics, and feeding regimens. Data regarding extremely low
birth weight infants (ELBW) could not be extrapolated.
In a meta-analysis of trial data, enteral probiotics supplementation significantly
reduced the incidence of severe NEC (stage II or more) [typical RR 0.32 (95% CI
0.17, 0.60)] and mortality [typical RR 0.43 (95% CI 0.25, 0.75]. There was no
evidence of significant reduction of nosocomial sepsis [typical RR 0.93 (95% CI 0.73,
1.19)] or days on total parenteral nutrition (TPN) [WMD -1.9 (95% CI -4.6, 0.77)].
The included trials reported no systemic infection with the probiotics supplemental
organism. The statistical test of heterogeneity for NEC, mortality and sepsis was
insignificant.
Reviewers' conclusions
Enteral supplementation of probiotics reduced the risk of severe NEC and mortality in
preterm infants. This analysis supports a change in practice in premature infants >
1000 g at birth. Data regarding outcome of ELBW infants could not be extracted from
the available studies; therefore, a reliable estimate of the safety and efficacy of
administration of probiotic supplements cannot be made in this high risk group. A
large randomized controlled trial is required to investigate the potential benefits and
safety profile of probiotics supplementation in ELBW infants.
58. The Role of Nutrition in
the Prevention and
Management of
BPDSeminars in Perinatology
30:200-208
59. Nutritional Intake
Preterm infants with BPD are at risk for undernutrition due to difficulties maintaining appropriate
nutritional intake
– as a result of co-morbidities (Carlson, 2004) eg swallowing dysfunction, fatigue during
feeding, GERD, dysfunction of other organ system eg NEC, prolonged TPN
– medically indicated fluid restriction (Carlson, 2004; Oh et al., 2005),
– and elevated energy expenditure (Bauer et al., 2003; Leitch & Denne, 2000).
– Use of dexamethasone
– Anemia of prematurity
– Medications eg methyl xanthines and beta sympthomimetics can increase energy
consumption
BPD patients can have increased energy expenditure up to 25% above total caloric needs
– Increased work of breathing
– Higher resting metabolic rates
61. Calories
Breast milk requires HMF, multivitamin and iron supplements
Alternatively use prem formula
– Provides additional calories, proteins, calcium, phosphorus and vitamins
Additional fat may be desirable
– Increases calories
– Less CO2 production than carbohydrates
– However, additional fat slows gastric emptying and may worsen GERD
Glucose polymers
– Provide additional 4kcal/g
– May cause hyperosmolar diarrhoea
Protein supplementation can be considered or provided by using a
high caloric formula eg 30 kcal/oz
62. Calcium, Phosphorus and Vit D
Osteopenia of prem more common in BPD
– Limited solubility of Ca and phosphorus in
TPN
– Low enteral intake
– Loop diuretics/urinary loss
Provide above via prem formula or
fortified BM
63. Nutrients
Vit A
– Deficiency associated with impaired clearance of lung
secretions, impaired water homeostasis across
tracheobronchial epithelium, loss of cilia, diminished
lung injury repair and lack of airway distensability
– Well documented to result in BPD/death in Vit A
deficiency (NICHD study).
– Dose of IM 5000 IU per dose 3x/week (12 doses) for
ELBW. Oral does not work.
Under study: inositol, Vit E
64. Discharge in BPD
67% continue to have growth failure post
discharge
Individualised nutrition plan
Continue 22kcal/oz prem formula for 6-8 months
Low salt/low volume/high calorie diet may be
necessary
Achieve solid intake slower than chronological
age, often tolerate spoon feeding (thicker
consistency) better than nipple (liquid). This may
begin at 3-4 mths post gestation
68. Early discharge with home support of gavage
feeding for stable preterm infants who have not
established full oral feeds 2008 Cochrane
Collaboration
Main results
Data from one quasi-randomised trial with 88 infants from 75 families were included
in the review.
Infants in the early discharge program with home gavage feeding had a mean
hospital stay that was 9.3 days shorter [MD -9.3 (-18.49 to -0.11)] than infants in the
control group. Infants in the early discharge program also had a lower risk of clinical
infection during the home gavage period compared with the corresponding time in
hospital for the control group [relative risk 0.35 (0.17 to 0.69)].
There were no significant differences between groups in duration and extent of
breast feeding, weight gain, re-admission within the first 12 months post discharge
from the home gavage program or from hospital, scores reflecting parental
satisfaction, or health service use.
Authors’ conclusions
Experimental evidence to evaluate the benefits and risks in preterm infants of early
discharge from hospital with home gavage feeding compared with later discharge
upon attainment of full sucking feeds is limited to the results of one small quasi-
randomised controlled trial.
High quality trials with concealed allocation, complete follow-up of all randomised
infants and adequate sample size are needed before practice recommendations can
be made.
69. Use of transitional formula: the
evidence
Post discharge Nutrition of Preterm Infants, Journal of Perinatology 2005; 25:S15–S16
feeding of specially designed post discharge formulas has
demonstrated better weight (at 9 but not at 18 months) and length
(at 9 and 18 months) as well as higher bone mineral content when
compared to term infant formula
– Lucas A, King F, Bishop NB. Postdischarge formula consumption in infants born preterm. Arch Dis Child 1992;67:691–2.
– Lucas A, Fewtrell MS, Morley R, Singhal A, Abbott RA, Isaacs E. Randomized trial of nutrient-enriched formula versus standard
formula for post discharge preterm infants. Pediatrics 2001;107:683–9.
the benefit appears restricted to males, a finding similar to that of
Cooke et al.
– Cooke RJ, Griffin IJ, McCormick K, Wells JC, Smith JS, Robinson SJ. Feeding preterm infants after hospital discharge: effect of dietary
manipulation on nutrient intake and growth. Pediatr Res 1998;43:355–60
From the NICHD network, data demonstrate that in virtually all
infants less than 1500 g, appropriate-for-gestational-age infants are
‘‘converted’’ to small for-gestational-age infants by 36 weeks
postmenstrual age.
Some recovery in these parameters has been reported
Chronic lung disease adds an additional burden as demonstrated by
73% of infants in one study experiencing a decrease in weight z
score between hospital discharge and 7 months
70. Use of transitional formula:
Guidelines
Post discharge Nutrition of Preterm Infants, Journal of Perinatology 2005; 25:S15–S16
Until more optimal strategies are developed, striving
toward achieving the best possible gain without
adverse effects may be appropriate.
Guideline:
<1800 g: 24 kcal/oz preterm infant formula
Transition to 22 kcal/oz at >1800 g if all growth
parameters are 25th percentile or greater and infant
is gaining 15 to 40 g/day
Transition from 22 kcal/oz to 20 kcal/oz term formula
at 4–6 months corrected gestational age if all growth
parameters are above 25th percentile
71. Nutrition Practice Care
Guidelines for Preterm Infants
In the Community (Revised
August 2006)
Developed by: Child Development and
Rehabilitation Center, Nutrition Services
Oregon Department of Human Services, Nutrition
& Health Screening – WIC Program Oregon
Pediatric Nutrition Practice Group
72. Referral Criteria
These “red flags” should alert the community nutritionist of the need for
further assessment, referral and follow-up
Anthropometric “Red Flags”:
• Weight loss or significant decline in percentile ranking (“falling away”
from expected growth curve percentile)
• Poor rate of weight gain for corrected age as listed below:
Age Weight Gain
term – 3 mos < 20 gm/day (< 5 oz/wk)
3 – 6 mos < 15 gm/day (< 3½ oz/wk)
6 – 9 mos < 10 gm/day (< 2 oz/wk)
9 – 12 mos < 6 gm/day (< 1½ oz/wk)
1 – 2 yrs < 1 kg or < 2 lbs in 6 mos
2 – 5 yrs < 0.7 kg or < 1½ lbs in 6 mos
73.
74.
75.
76.
77. VITAMIN-MINERAL SUPPLEMENTATION
Vitamins: Supplementation with a standard infant multivitamin (with
vitamins A, D, B1, B2, B3, B6, B12, C, and iron) is generally needed initially
after NICU discharge to meet the preterm infant’s vitamin needs, until the
infant is consuming larger volumes of feeds.
Vitamin D: Per the American Academy of Pediatrics (AAP), all infants fed
unfortified breast milk should continue to receive a supplement of 200 IU of
Vitamin D for the first year.
– This 200 IU of Vitamin D can be provided by continuing the 0.5 ml daily of the
standard infant multivitamin, or by changing to 0.5 ml daily of a tri-vitamin
supplement (vitamins A, C, and D). Infants receiving 17 oz. (500 ml) or more of
a vitamin D-fortified infant formula do not need any additional Vitamin D
supplementation.
Iron: Preterm infants have lower iron stores than term infants. By 2
months post birth (not 2 months corrected age), preterm infants should
have an intake of 2-4 mg iron/kg/day (up to a maximum of 40 mg/day)
from an iron-fortified infant formula and/or supplement. This iron dose
should be continued for the first year of life.
78.
79.
80.
81.
82.
83.
84.
85.
86.
87. Osteopenia of prematurity is most commonly seen in:
• Very-low-birth-weight infants (BW < 1500g).
• Any IUGR infant with a birthweight < 1800 g regardless of gestational age.
• Infants with chronic lung disease/bronchopulmonary dysplasia.
• Infants requiring long-term parenteral nutrition at birth.
• Infants on certain medications, including diuretics & corticosteroids, that affect
mineral absorption.
• Infants starting feedings of unfortified breastmilk or standard formula too early, or
soy formula.
Recommendation for checking labs:
• 1-month post-discharge for the infants born < 1500g and IUGR with birthweight <
1800 g.
• 1-month post-discharge if any of the labs at discharge (if known) are outside the
reference range.
• If the premie is transitioning to the breast or a term formula < 3-6 months
corrected age.
• If the premie has had marginal intake and slower growth.
Bone health can be assessed using the following labs.
•In the absence of other disease conditions, alkaline phosphatase provides an indirect
indicator of bone cell activity.
•Higher alkaline phosphatase along with lower calcium and phosphorus levels may
indicate a need for further assessment and supplementation. These labs are usually
done in the hospital setting, and may be done in the community up until 6-9 months
corrected age.
88.
89.
90.
91.
92.
93.
94.
95.
96.
97. One last example to put it all
together …
the ADHB (Auckland District Health
Board) guidelines
104. Nutrition Practice Care Guidelines for Preterm Infants In the Community. Revised August 2006.
Developed by Child Development and Rehabilitation Center, Nutrition Services, Oregon
Department of Human Services, Nutrition & Health Screening – WIC Program. Oregon Pediatric
Nutrition Practice Group
APPENDIX E: SELECTION OF FEEDING AT DISCHARGE
Feeding strategies for the preterm infant need to be evaluated on an individual basis. These guidelines are designed to help
the practitioner in making feeding selections to promote optimal nutrition. Birth weight, weight at discharge, and NICU course
are usually better predictors of risk than gestational age at birth. Breastfeeding after premature birth is recommended and
encouraged whenever possible. Lactation consultation is encouraged to promote successful breastfeeding and use of a breast
pump if needed.
1. High Risk – Very Low Birth Weight Infant
Category Definition:
• Birth weight < 1500gm (3.3 lbs)
• History of TPN and diuretics
• Demonstrates poor growth
• Poor intake (< 150 ml/kg/day)
• Elevated alkaline phosphatase (> 500 U/L) and/or low phosphorus (< 4)
Formula Feeding Recommendations:
• In majority of cases, these infants will need transitional formulas (EnfaCare or Neosure) until 9 months corrected age. If
change to a term formula, check labs and monitor growth.
• Continue on transitional formula unless:
o Infant cannot tolerate formula
o Excessive rate of weight gain
o Calcium and Phosphorus exceed normal limits
Breastfeeding Recommendations:
• Supplement breastfeeding with a transitional formula (Similac Neosure or Enfamil EnfaCare) until infant able to sustain
growth, ad lib milk intake, and lab values are within normal limits
• Discuss family’s breastfeeding goals in order to support breastfeeding while still maintaining infant’s growth and lab values.
105. Moderate Risk – Low Birth Weight Infant
Category Definition:
• Infant had BW > 1500 gm (3.3 lbs), has good growth, use of TPN and diuretics was minimal and alkaline
phosphatase level WNL
• Osteopenia evidenced by serum phosphorous <4mg/dl, alkaline phosphatase > 500 U/L
• Weight for corrected age is less than 5th percentile on CDC 2000 growth grids
• Infant has bronchopulmonary dysplasia/chronic lung disease with steroid use
Formula Feeding Recommendations:
• Provide transitional formulas (EnfaCare or Neosure) to 9 months corrected age.
• Continue on transitional formula unless:
o Infant cannot tolerate formula
o Excessive rate of weight gain
o Calcium and Phosphorus exceed normal limits
o If change to a term formula, check labs and monitor growth
Breastfeeding Recommendations:
• Supplement breastfeeding with a transitional formula (Similac Neosure or Enfamil EnfaCare) until infant able to
sustain growth, ad lib milk intake, and lab values are within normal limits
• Discuss family’s breastfeeding goals in order to support breastfeeding while still maintaining infant’s growth and
lab values.
106. Low Risk – Low Birth Weight Infant
Breastfeeding Recommendations:
• Breastfeed on demand.
• If milk intake or supply is insufficient, as evidenced by slow growth on CDC growth grid, assess the
need for lactation support or supplementation with standard formula such as Enfamil Lipil or Similac
Advance.
Formula Feeding Recommendations:
• Offer standard 20 kcal/oz iron fortified infant formula such as Enfamil Lipil or Similac Advance until 1
year corrected age.
Category Definition:
• Birth weight > 2000 gm (4.4 lbs)
