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?