Study Background
Why worry about feeding?
Enteral feeding may result in:
 Compromise of diaphragmatic function
 Reduced FRC & compliance, ↑PaCO2
(Heldt 1988, Blonheim et al 1993)
 Apnoea
 Gastro-oesophageal reflux
 NEC
Why worry about NEC?
• Still affects 7% of VLBW infants (Lemons
et al, Pediatrics 2001)
• Has >20% mortality (in BPSU surveys
1981-2 & 1993-4)
• Has drastic effects on nutrition, cholestasis
• 90% of babies who develop NEC are
receiving enteral feeds
Does NEC occur more frequently in
IUGR Babies?
• Early case-control studies matched for weight
• Case-control study of 74 cases of NEC in preterm
infants: at 30-36 weeks GA, bw<10th c,
significant factor: OR 6 (1.3-26)
– Beeby and Jeffrey. 1991, ADC:67:432-5
• Observation study Oxford 1985-91: 69 cases of
definite/proven NEC. At 30-36 weeks 71% <10th
centile (49% overall)
– McDonnell and Wilkinson. Sem Neonatol 1997
Why should NEC occur more
frequently in IUGR Babies?
• Pathogenesis of NEC may include enteral
feeding, gut ischaemia, bacterial infection
– Santulli et al. Paediatrics 1975;55:376-87
• Abnormal gut blood flow in IUGR - absent
or reversed end-diastolic flow velocities on
Doppler in UA or mesenteric vessels
• Hypoxic/ischaemic damage to gut mucosa
• Reperfusion injury
• Alteration in postnatal GI function
Normal Doppler blood flow in Umbilical Artery
Systole
Diastole
Umbilical Artery Doppler: Absent flow in diastole
Antenatal Doppler – reversed end-diastolic flow
Does NEC occur more often after
fetal AREDFV?
• 14 reviews comparing NEC rates in babies
born after AREDFV
• 9 studies showed excess of NEC in babies
with AREDFV: OR 2.13 (95%CI 1.49-3.03)
• Dorling J, Kempley S, Leaf A. Feeding growth restricted
preterm infants with abnormal antenatal Doppler results.
Arch. Dis. Child. Fetal Neonatal Ed. 2005; 90: F359-F363
Dorling, J et al. Arch. Dis. Child. Fetal Neonatal Ed. 2005;90:F359-F363
Copyright ©2005 BMJ Publishing Group Ltd.
Blood flow, hypoxia and feeding
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Feeding increases intestinal blood flow
Feeding also increases intestinal oxygen
consumption
Hypoxia has a more significant effect on
intestinal oxygen delivery when feeds given
Less mature animals may have immature
autoregulation and a reduced ability to increase
oxygen uptake
Postnatal haemodynamic changes
in SGA infants
Reduced velocity of blood flow in the SMA
• Kempley et al 1991
• Martinussen et al 1997
• Maruyama et al 2001
Impaired response to enteral feeding of SMA
blood flow velocity
First day SMA blood flow velocity in SGA infants and controls
SMA blood flow velocity (cm/s)
60
50
40
30
20
10
0
SGA
AREDF
Weight
GA
Controls
SGA
EDF+
Weight
GA
Controls
Strategies to prevent NEC?
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Enteral antibiotics
Enteral immunoglobulins
Delay enteral feeding
Slow increase in enteral feeds
Non-nutritive feeds
TPN
Is there any evidence to support
these feeding strategies?
• Systematic reviews in Cochrane Library
– “Early vs delayed initiation of progressive
enteral feeding for LBW and preterm…”
– “Rapid vs slow advancement of feeding to
promote growth and prevent NEC…..”
– “Minimal enteral nutrition to promote feeding
tolerance and prevent morbidity…”
“Early vs delayed initiation of progressive enteral
feeding for parenterally fed LBW or preterm
infants” Kennedy and Tyson 1999
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Only 2 studies: total 72 babies (60 and 12)
All had PN
Early < 4days; late 4days
Progressive feeds within 72 hours of
starting
• Early: less PN, less sepsis investigation
• No difference NEC, wt gain, LOS
“Rapid vs slow advancement of feeding to
promote growth and prevent NEC in parenterally
fed preterm infants” Kennedy and Tyson 1998
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Rapid: 20-35 cc/kg/day
Slow: 10-20 cc/kg/day
3 studies including 369 babies; all had PN
Reduced days to full enteral feeds and
regain birthweight
• No difference NEC or length of stay
“Minimal enteral nutrition to promote feeding
tolerance and prevent morbidity…”
Tyson JE and Kennedy KA 1997
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MEN = 12-24 cc/kg/day
Started day 1 – day 8
All babies <1500g or < 33 weeks
MEN 5-10 days
8 studies – 380 patients
– Reduction in days to full feeds (wmd 2.7) and
LOS (wmd 15.6)
– No difference in NEC
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)
Position of equipoise
• IUGR babies with AREDFV on antenatal
Dopplers do have increased risk of NEC
• BUT…no evidence that early or late
initiation of feeds is of benefit
• AND…delaying feeds may increase risks of
sepsis, cholestasis, BPD
• AND increase duration of intensive care
and length of hospital stay