Title: Prof Sanjay Patole, MD, DCH, FRACP, MSc, DrPH
1Feeding the preterm IUGR infant
- Prof Sanjay Patole, MD, DCH, FRACP, MSc, DrPH
- Centre for Neonatal Research and Education
- KEM Hospital for Women, University of Western
Australia Perth
2Feeding preterm IUGR infants
- Experimental studies show that hypoxia reduces
intestinal blood flow and oxygen delivery through
adrenergic vasoconstriction. - Nowicki et al 1988
- ? Oxygen extraction can compensate for a 30
reduction in gut blood flow, but enteral feeding
reduces the ability of oxygen extraction to
compensate for the effects of hypoxia. - Bulkley et al 1985, Szabo et al 1987
- Metabolic demands of enteral feeds increase O2
consumption by the intestine. - Nowicki et al 1983
3Feeding preterm IUGR infants
- SMA and Coeliac axis flow is significantly
reduced on D1 and the recovery in the baseline
flow is slow during the 1st week of life in IUGR
infants - Despite the recovery in baseline SMA and Coeliac
axis flow, the dynamic response to 1st feed is
still impaired in IUGR infants - Gamsu 1997, Maruyama 2001, Murdoch 2003
4Feeding preterm IUGR infants Perth data
- 38/220 (17.3) neonates lt 28 weeks during 2 year
period had IUGR. - Mean (IQR) age at start of feeds 7 (5-10) vs. 5
(4-8) days, p??0.005 - Mean (IQR) age at 1?ml/2hourly feeds 12 (8-15)
vs. 9 (7-13) days, p??0.034 -
- Shah et al JMFN Med 2014
5Feeding preterm IUGR infants
- Median (IQR) postnatal age at FEF
(150?ml/kg/day) 32 (21-40) vs. 24 (17-31) days,
p??0.009 - Postnatal growth restriction 73 vs. 45,
p??0.003 - Definite NEC 18/220 (8.1)
- Conclusion Optimising enteral nutrition in
extremely preterm IUGR neonates is a difficult
proposition - Shah et al JMFN Med 2014
6Preterm IUGR infants and abnormal Dopplers
- Independent case series (N14)
- All NEC AREDF 85/659 vs Control 66/1178
- OR 2.13 (95 CI 1.49 to 3.03)
- Confirmed NEC (6 studies)
- OR 6.9 (95 CI 2.3 to 20)
- Dorling et al. ADC2005
7- Santulli theory for pathogenesis of NEC Triad of
ischaemia, bacteria, and substrate - Santulli et al. Pediatrics 1975
- Prolonging small feeding volumes early in life
decreases the incidence of NEC in VLBW infants. - Berseth et al. Pediatrics 2003
8Early feeding advancement in VLBW infants with
IUGR and ? UA resistance
- 124 inborn VLBW infants enrolled in a prospective
trial evaluating early enteral nutrition after a
standardized feeding protocol (daily feed
increment 16 ml/kg) - Feeding tolerance assessed by age at FEF (150
ml/kg/day) - Mihatsch et al. JPGN2002
9Results
- FEF achieved at 15 days (12-21 days) of age for
all infants. - IUGR FEF 14 (12-21) days, ? UA resistance
FEF 14 (11-16) days, and brain sparing FEF
15 (14-20) days were not associated with early
feed intolerance. - Conclusion VLBW infants with IUGR, ? UA
resistance, and brain sparing tolerated enteral
feeds as well as AGA VLBW infants.
10Early versus delayed MEF and risk for NEC in
preterm IUGR infants with abnormal Dopplers.
- Aim Assess the effect of early (5 days) vs.
delayed (6 days) MEF on the incidence of NEC and
feed intolerance in preterm IUGR infants with
abnormal Dopplers. - Design Randomized, non-blinded pilot trial
Early vs. Delayed MEF in addition to PN
within 48 hours -
- Karagianni et al. 2010 May
11Results
- 81/84 enrolled infants completed the trial
- 40 Early 2 (1-5) vs. 41 Delayed MEF 7 (6-14)
days - No significant difference in NEC (p0.353) and
feeding intolerance (p0.533)
12Results
- Birth weight was an independent risk factor for
NEC in both groups. - Early MEF may not have a significant effect on
NEC or feed intolerance in preterm IUGR infants
with altered Dopplers.
13Predictors of NEC in preterm IUGR neonates
- Even when Doppler variables are taken into
consideration, birthweight remains the
predominant risk factor for NEC. - Manogura AC et al. Am J Obstet Gynecol. 2008
14- Early vs. delayed enteral feeding for preterm
growth-restricted infants a randomized trial - Leaf et al. Pediatrics 2012 May
15Background
- Preterm IUGR infants are at increased risk of NEC
and delayed initiation of feeds - No evidence that this delay is beneficial and
might further compromise nutrition and growth
16Methods
- Infants with gestation lt35 weeks, BW lt10th
centile and abnormal UA Doppler waveforms
randomly allocated to - Start feeds "Early" (D2) or "Late" (D6) after
birth - Feeds ? gradually by a feeding protocol, equal
rate of increase for both groups - Primary outcomes Time to FEF sustained for 72
hrs and NEC
17Sample size estimation
- Unpublished data from a UK regional database of
VLBW revealed an SD of 9 days in the time to
reach FEF - 380 infants needed to show a 3 day difference in
time to FEF with 90 power - NEC15, so recruiting 400 infants would be
sufficient to show a 50 change in the incidence
of NEC with 60 power
18Results
- 404 infants from 54 hospitals in UK and Ireland
(202/group) - Median gestation 31 weeks
- FEF (Median) Early 18 vs. Late 21 days (HR
1.36 95 CI 1.11-1.67) - All Stage NEC Early 18 vs. Late 15 (RR 1.2
95 CI 0.77-1.87) - Stage II/III NEC 8 in both groups
- Early feeds Shorter duration of TPN and
high-dependency care, ? cholestasis, and ? SD
score for weight at discharge
19Conclusion
- Early introduction of feeds in preterm IUGR
infants resulted in earlier achievement of FEF
without increasing the risk of NEC
20Applicability of ADEPT trial results
- Gestation lt29 weeks 44 vs. 42 infants
- Birth weight lt1000 grams 86 vs. 105 infants
- Birth weight lt 750 grams 33 vs. 41 infants
- Not powered adequately for detecting a minimum
significant change in incidence of NEC, the real
concern - Enrolment from 64 centres
- No real justification for late starting of feeds
(after 6 days)
21Post-hoc analysis ADEPT subgroup
- IUGR neonates lt29 weeks failed to tolerate even
the careful feeding and reached FF significantly
later than predicted - Median (IQR) age at FEF in lt29 vs 29 weeks
- 28 (22-40) vs. 19 (17-23) days, HR 0.35 (95 CI
0.3 to 0.5) - Incidence of NEC significantly higher in lt29 vs
29 weeks - 32/83 (39) vs. 32/312 (10), RR 3.7, (95 CI
2.4 to 5.7) -
- Kempley et al. ADC 2013 Aug
22Other risk factors
- PDA
- Ibuprofen
- Phototherapy
- CPAP
- Proinflammatory cytokines (PIH)
- Oxidative stress
- Sepsis (neutropenia)
- Polycythemia
23Minimising the risk of NEC in IUGR neonates
- Early trophic enteral feeds
- Early preferential use of mothers milk
- PDHM if mothers milk is unavailable/Avoid
formula - Feeding protocol (Conservative vs. Aggressive)
- Ideal vs realistic nutritional goals
- Prevention and treatment of sepsis
- Probiotic supplementation
24NEC Unusual presentation in preterm IUGR
- No significant abdominal distension, minimal bile
stained gastric residuals, no/no significant
pneumatosis but - Significant widespread necrosis of the gut on
autopsy -
25Feeding preterm IUGR infants lt28 weeks
- Start colostrum as soon as available (Day 0)
- Early trophic feeds lt10 ml/kg/day, Duration 5
days - Nutritional feeds Start at 15 ml/kg/day and ? by
15 ml/kg/day - Consider continuous feeds for persistent feed
intolerance - Reach 60 ml/kg/day to promote gut development and
function - Worsening volume and colour of gastric residuals
Take a break!! - Clinical examination, and awareness of coexisting
risk factors for NEC are important - Probiotic supplementation (Will they work?)