1. 2 Birmingham Children’s Hospital, Birmingham
Slow advancement of enteral feed volumes to prevent necrotising enterocolitis in very low birth weight infants: systematic review.
1Morgan J, 1,2 Young L, 1 McGuire W. 1 Centre for Reviews and Dissemination, Hull York Medical School, University of York.
2 Birmingham Children’s Hospital, Birmingham
Partly funded by the National Institute for Health Research Academic Clinical Fellowship Programme

2. Is it really important though?
15 million
11%
1 million
7% of babies born in UK, or 70,000 The global average preterm birth rate is 11%, that’s 15 million preterm babies every year 3 million infants die in the first 28 days of life
1 million die as a result of preterm birth complications

4. 5% of preterm births

5. 5% of preterm births
20% mortality

6. Stay in hospital longer Get more infections More long-term disability
5% of preterm births
20% mortality
Grow more slowly
Stay in hospital longer
Get more infections
More long-term disability
Compared with their peers, infants who develop NEC have a higher incidence of long-term neurological disability, which may be a consequence of infection and under-nutrition during a critical period of brain development (Stoll 2004; Soraisham 2006; Rees 2007; Pike 2012).

7. Prolonged PN
Infections
Reduce NEC?

8. Prolonged PN
Infections
Reduce NEC?

9. Prolonged PN
Infections
Reduce NEC? enteral feeding is introduced earlier and feeding volumes advanced more quickly tend to have higher incidences of NEC (Uauy 1991).
Observational studies have suggested that delaying the introduction of enteral feeds beyond the first few days after birth, or increasing the volume of feeds by less than about 20 ml/kg to 24 ml/kg body weight each day, is associated with a lower risk of developing NEC in very preterm or VLBW infants (Brown 1978; McKeown 1992; Patole 2005; Henderson 2009).

10. 395g
Slow postnatal growth has been associated with long term growth restriction, neuro-developmental impairment and poorer educational outcomes in later childhood, and cardiovascular disease, obesity and insulin resistance in later life.

11. Slow
Prolonged PN
Infections
Reduce NEC?

12. Fast
Prolonged PN
Infections
Reduce NEC?

13. Results Six trials 618 infants
Slow advancement of 15 ml/kg to 20 ml/kg
Faster advancement of 30 ml/kg to 35 ml/kg.
Good methodological quality
included – mostly very preterm and very low birth weight infants.

14. Does not increase the risk of NEC
Advancing enteral feeds at 30 ml/kg to 35 ml/kg does not increase the risk of NEC in very preterm or VLBW infants.
Increasing the volume of enteral feeds at slow rates (less than 24 ml/kg/day) results in several days delay in the time taken to regain birth weight and establish full enteral feeds.

15. Takes longer to reach full feeds Longer to regain birthweight ££££££ IUGR, borderline increase mortality in slow group
Slow expensive tortoise

16. Research Question
To assess and compare the effects of a fast (30 ml/kg/day) and a slow (18 ml/kg/day) increase in milk feed volumes on survival of very preterm (<32 weeks) or VLBW (<1,500 g) infants without moderate or severe disability at 24 months of age corrected for prematurity

19. Why is this important?

21. Future research questions
How fast should we increase feeds?
Should we feed IUGR/SGA infants differently to non-IUGR/SGA infants?
What are the longterm outcomes e.g neurological?
Does rapid growth have adverse effects?

22. References to included studies
Bisquera 2002
Brown 1978
Caple 2004
Flidel-Rimon 2004
Guthrie 2003
Henderson 2009
Holman 1997
Karagol 2012
Krishnamurthy 2010
McKeown 1992
Mukhopadhyay 2014
Patole 2005
Pike 2012
Rayyis 1999
Rees 2007
Salhotra 2004
Soraisham 2006
Stoll 2004
Uauy 1991

23. Methods • Cochrane systematic review:
Search: CENTRAL (The Cochrane Library, Issue 8, 2014), MEDLINE, EMBASE, and CINAHL (until Sep 2014), conference proceedings, and previous reviews.
Data collection and analysis: Standard method of the Cochrane Neonatal Group, with separate evaluation of trial quality and data extraction by two authors, and synthesis using a fixed effect model for meta-analysis.

24. Nectrotising enterocolitis (NEC)
Acute intestinal necrosis of unknown aetiology, affects about 5% of very preterm (<32 wks) or very low birth weight (VLBW) (<1500g) infants (Holman 1997), mortality rate is more than 20%.
Infants who develop NEC experience more nosocomial infections, have lower levels of nutrient intake, grow more slowly, and have longer durations of intensive care and hospital stay than gestation-comparable infants who do not develop NEC (Bisquera 2002; Guthrie 2003)
Compared with their peers, infants who develop NEC have a higher incidence of long-term neurological disability, which may be a consequence of infection and under-nutrition during a critical period of brain development (Stoll 2004; Soraisham 2006; Rees 2007; Pike 2012).

25. How do you feed premature infants?Or
Breast feed
Via naso-gastric tube Or
Expressed breast milk
Formula milk

26. Slow versus faster rates of feed advancement: effect on incidence of NEC.
STUDY/SUBGROUP
Risk Ratio M-H, Fixed (95% CI )
All trials
Mukhopadhyay
0.50 (0.05, 4.94)
Karagol
1.25 (0.36, 4.36)
Krishnamurthy
0.50 (0.05, 5.34)
Salhotra
0.21 (0.01, 4.12)
Caple
0.57 (0.11, 3.01)
Rayyis
1.44 (0.63, 3,32)
Subtotal
0.96 (0.55, 1.70)
Trials with most infants SGA/IUGR
0.50 (0.05, 4,94)
0.34 (0.06, 2.04)
0.01
0.1 1 10
100

27. Slow versus faster rates of feed advancement: effect on mortality.
STUDY/SUBGROUP
Risk Ratio M-H, Fixed (95% CI )
All trials
Rayyis
0.59 (0.10, 3.46)
Salhotra
1.78 (0.83, 3.81)
Krishnamurthy
1.50 (0.45, 4.99)
Karagol
1.33 (0.32, 5.63)
Mukhopadhyay
7.00 (0.39, )
Subtotal
1.57 (0.92, 2.70)
Trials with most infants SGA/IUGR
2.12 (1.02, 4.47)
0.01
0.1 1 10
100