Position of equipoise on ‘when to start’
description
Transcript of Position of equipoise on ‘when to start’
![Page 1: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/1.jpg)
![Page 2: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/2.jpg)
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
![Page 3: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/3.jpg)
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
![Page 4: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/4.jpg)
Where does current practice come from?
![Page 5: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/5.jpg)
• 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
![Page 6: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/6.jpg)
• 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
![Page 7: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/7.jpg)
‘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
![Page 8: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/8.jpg)
‘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
![Page 9: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/9.jpg)
‘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
![Page 10: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/10.jpg)
‘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
![Page 11: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/11.jpg)
‘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
![Page 12: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/12.jpg)
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
![Page 13: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/13.jpg)
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
![Page 14: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/14.jpg)
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
![Page 15: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/15.jpg)
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
![Page 16: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/16.jpg)
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.
![Page 17: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/17.jpg)
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..
![Page 18: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/18.jpg)
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.
![Page 19: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/19.jpg)
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
![Page 20: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/20.jpg)
Not Not reasons for deviation
• type of milk available
• ventilation status
• presence of an UAC / UVC
![Page 21: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/21.jpg)
Milk feeding and ventilation
milk feed do not milk feed
2
13
![Page 22: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/22.jpg)
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.
![Page 23: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/23.jpg)
Milk feeding and UAC
milk feed with UAC do not milk feed with UAC
2
13
![Page 24: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/24.jpg)
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
![Page 25: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/25.jpg)
A Breast Feeding Friendly Trial
• Please encourage EBM as much as possible!
![Page 26: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/26.jpg)
Thank you for your attention
Any Questions?
![Page 27: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/27.jpg)
![Page 28: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/28.jpg)
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
![Page 29: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/29.jpg)
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
![Page 30: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/30.jpg)
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.
![Page 31: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/31.jpg)
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
![Page 32: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/32.jpg)
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)
![Page 33: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/33.jpg)
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
![Page 34: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/34.jpg)
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
![Page 35: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/35.jpg)
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
![Page 36: Position of equipoise on ‘when to start’](https://reader036.fdocuments.us/reader036/viewer/2022062314/56814897550346895db5ac76/html5/thumbnails/36.jpg)
Thank you for your attention
Any Questions?