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Position of equipoise on ‘when to start’
• IUGR babies with AREDFV on antenatal Dopplers do have an increased risk of NEC
• BUT…no evidence that delaying feeds is of benefit
• AND…delaying feeds may increase;- – sepsis, cholestasis, chronic lung disease,
duration of intensive care and length of hospital stay
Should one delay feeds?The ‘evidence’
• Cochrane review • ‘early’ < 4 days• 2 small studies included • 72 preterm infants only• No differences seen for
– days feedings held, weight gain, conjugated jaundice, necrotizing enterocolitis and death.
• Kennedy KA, Tyson JE. Early versus delayed initiation of progressive
enteral feedings for parenterally fed low birth weight or preterm infants
Where does current practice come from?
• Historical comparison in late 70s • Switch from aggressive to conservative
management
• Brown and Sweet (Mount Sinai N.Y)• Proven NEC in
– 14 / 1,745 LBW infants 1970 – 1974– 1 / 932 LBW infants 1974 - 1978
• Started feeds at 5-7 days in ‘at risk’ infants (not defined)
• 3 hourly feeds of water, then diluted formula
• Increased volume and concn over 16 days
• No statistics in the paper!
• Previous approach not described
‘early’ ‘late’
0-24 hours(day 1)
Nil by mouth Nil by mouth
24-48 hours(day 2)
Start milk feeds according to tables 1 & 2
Nil by mouth
48-119 hours(day 3-5)
Progress with feeding according to tables 1 & 2
Nil by mouth
120-143 hours(day 6)
Progress with feeding according to tables 1 & 2
Start milk feeds according to tables 1 & 2
144 hours onwards (day 7+)
Progress with feeding according to tables 1 & 2
Progress with feeding according to tables 1 & 2
ADEPT Trial feeding regimes
‘early’ ‘late’
0-24 hours(day 1)
Nil by mouth Nil by mouth
24-48 hours(day 2)
Start milk feeds according to tables 1 & 2
Nil by mouth
48-119 hours(day 3-5)
Progress with feeding according to tables 1 & 2
Nil by mouth
120-143 hours(day 6)
Progress with feeding according to tables 1 & 2
Start milk feeds according to tables 1 & 2
144 hours onwards (day 7+)
Progress with feeding according to tables 1 & 2
Progress with feeding according to tables 1 & 2
ADEPT Trial feeding regimes
‘early’ ‘late’
0-24 hours(day 1)
Nil by mouth Nil by mouth
24-48 hours(day 2)
Start milk feeds according to tables 1 & 2
Nil by mouth
48-119 hours(day 3-5)
Progress with feeding according to tables 1 & 2
Nil by mouth
120-143 hours(day 6)
Progress with feeding according to tables 1 & 2
Start milk feeds according to tables 1 & 2
144 hours onwards (day 7+)
Progress with feeding according to tables 1 & 2
Progress with feeding according to tables 1 & 2
ADEPT Trial feeding regimes
‘early’ ‘late’
0-24 hours(day 1)
Nil by mouth Nil by mouth
24-48 hours(day 2)
Start milk feeds according to tables 1 & 2
Nil by mouth
48-119 hours(day 3-5)
Progress with feeding according to tables 1 & 2
Nil by mouth
120-143 hours(day 6)
Progress with feeding according to tables 1 & 2
Start milk feeds according to tables 1 & 2
144 hours onwards (day 7+)
Progress with feeding according to tables 1 & 2
Progress with feeding according to tables 1 & 2
ADEPT Trial feeding regimes
‘early’ ‘late’
0-24 hours(day 1)
Nil by mouth Nil by mouth
24-48 hours(day 2)
Start milk feeds according to tables 1 & 2
Nil by mouth
48-119 hours(day 3-5)
Progress with feeding according to tables 1 & 2
Nil by mouth
120-143 hours(day 6)
Progress with feeding according to tables 1 & 2
Start milk feeds according to tables 1 & 2
144 hours onwards (day 7+)
Progress with feeding according to tables 1 & 2
Progress with feeding according to tables 1 & 2
ADEPT Trial feeding regimes
Day of initial milk feeding
012345678
a b c d e f g h I j k l m n o
hospital
day
Dorling & McClure 1999 East Anglian SURVEY
Day of
feedingVolume of milk according to birth weight (ml/kg/HOUR)
<600g 600-749g 750-999g 1000-1249g
1250g
1 0.5 0.5 0.5 0.5 1.0
2 0.5 0.5 0.5 1.0 1.5
3 0.5 1.0 1.0 1.5 2.0
4 1.0 1.5 1.5 2.0 2.5
5 1.5 2.0 2.0 2.5 3.0
6 2.0 2.5 2.5 3.0 3.5
7 2.5 3.0 3.0 3.5 4.0 - 4.5
8 3.0 3.5 3.5 4.0 - 4.5 5.0 - 5.5
9 3.5 4.0 4.0 - 4.5 5.0 - 5.5 6.0 - 6.25
10 4.0 4.5 - 5.0 5.0 - 5.5 6.0 - 6.25
11 4.5 - 5.0 5.5 - 6.0 6.0 - 6.25
12 5.5 - 6.0 6.25
13 6.25
14 Increase as required
South West Neonatal Forum
Day of
feedingVolume of milk according to birth weight (ml/kg/DAY)
<600g 600-749g 750-999g 1000-1249g
1250g
1 12 12 12 12 24
2 12 12 12 24 36
3 12 24 24 36 48
4 24 36 36 48 60
5 36 48 48 60 72
6 48 60 60 72 84
7 60 72 72 84 96 - 108
8 72 84 84 96 - 108 120-132
9 84 96 96-108 120-132 144-150
10 96 108-120 120-132 144-150
11 108-120 132-144 144-150
12 132-144 150
13 150
14 Increase as required
South West Neonatal Forum
Why not increase faster?
• Schedules developed from Southwest practice
• mid point of a ‘reasonable’ approach
• ‘too fast’ might lead to accusation of raised NEC not representative of UK experience
Milk types
• Choice of milk – Mother’s own breast milk, – Donated breast milk– Infant formula (preterm / term)
• Advise infants with gestation <34 weeks to be fed preterm formula within one week of starting milk.
• BMF if additional nutrition required once baby tolerating > 150ml/kg/day.
Exclusions and Deviations
• Withholding feeds
• or deviating from feeding schedule
• for feed intolerance or clinical deterioration
• At local clinician’s discretionAt local clinician’s discretion..
Exclusions and Deviations
• Gastric residuals common.
• Providing the infant is well and has no abnormal abdominal signs it is usually
• Safe to continue with enteral feeds when gastric aspirate is 2-3 ml or less
• (2 ml if <750 grams birth weight)
– Mihatsch et al. J Pediatr Gastroenterol Nutr 2002;35:144-8.
Restarting after exclusion or Deviation
• Either – restart from day 1 of schedule
• or– re-start at the volume previously tolerated
then increase as schedule
• or – hold for one or more days at a certain
volume and then increase as schedule
Not Not reasons for deviation
• type of milk available
• ventilation status
• presence of an UAC / UVC
Milk feeding and ventilation
milk feed do not milk feed
2
13
UAC presence: the ‘evidence’
• 1 Small trial only• 29 infants: unable to exclude effect on
NEC!• Cohort papers significant confounding
data (sick infants need a UAC)
• Davey, J Pediatr 1994. Feeding premature infants while low umbilical artery catheters are in place: a prospective, randomized trial.
Milk feeding and UAC
milk feed with UAC do not milk feed with UAC
2
13
Breast milk better than formula (n=343)
McGuire, Anthony Arch Dis Child Fetal Neonatal Ed 2003. Donor human milk versus formula for preventing necrotising
enterocolitis in preterm infants: systematic review.
of NEC
A Breast Feeding Friendly Trial
• Please encourage EBM as much as possible!
Thank you for your attention
Any Questions?
Speed of advance
• Kennedy & Tyson. Rapid versus slow rate of advancement of feedings for promoting growth and preventing necrotizing enterocolitis in parenterally fed
low-birth-weight infants (Cochrane Review).
• 369 babies from three trials
• > 20 v < 20 cc/kg/day increase
Speed of advance
• faster increase in feed volumes
– reduction in days to full enteral feeding
– less days to regain birth weight
– NO effect on NEC
• RR = 0.90
• 95% CI 0.46 - 1.77
Trophic feeds / MEF etc
• Stimulate endocrine and motor gut function
• 10- 20 ml/kg/day for > 48 hours
• Cochrane study of 6 trials
• Tyson JE, Kennedy KA. Minimal enteral nutrition for promoting feeding tolerance and preventing morbidity in parenterally fed infants.
MEF Cochrane review
• Outcomes significantly affected by MEF – length of stay:
• WMD 15.6 days less stay in MEF group (95% CI 8.5 to 22.8)
– days to full feeding: • WMD 2.7 days less in MEF group
(95% CI 0.98 to 4.4).
• No difference in NEC or death rates
• last updated in 1997: 3 studies since
Further studies on MEN
• Schanler– n=171, NEC 13 in MEF, 10 controls
• McClure– n= 100, NEC 1 in MEF, 2 controls
• Van Elberg– IUGR infants, n=42, NEC 0 in MEF, 1 control
• Added to previous meta-analysis: NEC 10.5% in MEF, 9.4% controls (RR 1.07, 95%CI 0.84-1.36)
ADEPT - exclusions
• Major congenital abnormality
• Twin-twin transfusion
• Intra-uterine or exchange transfusion
• Rhesus haemolysis
• Multi-organ failure prior to randomisation
• Inotrope support prior to randomisation
• Already received enteral feed
ADEPT outcomes
• Primary outcomes– Time to reach full enteral feeds (for 72 hours)– NEC
• Secondary outcomes– Death– Duration of level 1 and level 2 IC– Growth: wt and OFC z-scores at 36w & d/c– Sepsis, cholestasis, bowel perforation, CLD
ADEPT sample size
• Time to reach full feeds– data taken from East Anglia– 380 babies needed to show difference of
3 days with 90% power
• NEC– Incidence approx 15%– 400 babies needed to show reduction to
7.5% with 60% power
Thank you for your attention
Any Questions?