1. Probiotics- 2 year experience Anitha James Royal Gwent hospital

2. Background Necrotizing enterocolitis (NEC) is a major cause of morbidity and mortality in preterm infants Affects 6-7% of VLBW infants Mortality 20-30% in VLBW infants Long term morbidity: Probiotics are live micro-organisms when administered in adequate amounts confer a health benefit on the host – Improved gut barrier – Enhanced mucosal IgA response – improve gut motility – Increased production of anti inflammatory cytokines

3. Background Updated Cochrane review RCTs in 2014 – (24 RCTs; 5529 neonates) Probiotics supplementation significantly reduces risk of stage II or greater NEC (RR: 0.43, 95% CI: 0.33,0.56) all-cause mortality (RR: 0.65; 95% CI: 0.52, 0.81) Alfaleh K et al.Cochrane systematic review 2014

4. Probiotics for infants < 1500 g: Preventing severe NEC (stage II-III) NNT 25 Alfaleh K et al.Cochrane systematic review 2014

5. Probiotics for infants < 1500 g: Reducing mortality NNT 33 Alfaleh K et al.Cochrane systematic review 2014

6. Species of probiotic: Prevention of severe NEC Alfaleh K et al.Cochrane systematic review 2014

7. Benefits of probiotics on enteral nutrition in preterm neonates: systematic review Primary outcome of interest – the time to establish full enteral feeds (TFEFs) Secondary outcomes – the time to regain birth weight – number of episodes of feed intolerance – duration of hospitalization Athalye-Jape et al. Am J Clin Nutr 2014;100:1508-19

8. Benefits of probiotics on enteral nutrition in preterm neonates: systematic review In the probiotic group – shorter time to full enteral feeds – fewer episodes of feed intolerance – better weight gain and growth velocity – decreased transition time from orogastric to breast feeds – increased postprandial mesenteric flow No adverse effects of probiotic supplementation Athalye-Jape et al. Am J Clin Nutr 2014;100:1508-19

9. Time to full feeds Athalye-Jape et al. Am J Clin Nutr 2014;100:1508-19

10. Time to full feeds Athalye-Jape et al. Am J Clin Nutr 2014;100:1508-19

11. Recent interventions in neonatology InterventionOutcomeSize effectNo of babies iNO for HRF in term infants Mortality Need for ECMO NS RR 0.61 (0.51-0.72) 1469 Hypothermia for HIEMortality Mortality or NDI RR 0.75 (0.63-0.88) RR 0.76 (0.69-0.84) 638 506 Antenatal steroid for preterm MortalityRR 0.77 (0.67-0.89)4269 Probiotics for preterm infants Mortality NEC RR 0.55 (0.40-0.75) RR 0.40 (0.29-0.55) 2495 4089 Janvier et al. Acta Paediatrica 2012

12. Interventions reducing the risk of NEC and death in preterm neonates Shlomai NO et al. Neonatology 2014;105:64-70

13. Probiotics use among VON units VON data 2014

14. Probiotics use among VON units VON data 2014

15. Are probiotics being used in your NICU?

16. Infloran Contains Lactobacillus acidophilus and Bifidobacterium bifidus Infloran: 10 9 bacilli LBA and BBB in 250mg Dose is 125mg twice daily Prescribed as drug for quality control and safety reasons Capsule contents dissolved in 1ml water, 0.5ml administered as a bolus Started when feeds of 0.5ml tolerated

17. Infloran Introduced in April 2013 PINC UK: : Probiotics In Newborns Collaboration Eligibility – Infants born <32 weeks – Infants with birth weight <1500 grams

18. Results 2013-2014 2014-2015 Number9378 Probiotics given8069 Gestation (median) weeks 27 Birth weight (median) grams 6781082

19. Study group Probiotics received Age at start (Median)6 days Age at start (Min)1 day Age at start (Max)38 days Duration of administration of probiotics: Median29 days Min1 day Max63 days

20. Reason for non-administration 22/171 (13%) – Died before starting feeds – Transferred out before feeds started – >34 weeks when feeds started – Missed

21. Outcomes 2013-142014-15 Eligible infants9378 Probiotics given8069 NEC ≥ stage2112 Deaths (all causes)74 Positive blood cultures 118

22. Causes of death 2014: 4 deaths (4/78) – Extreme prematurity:2 – Hydrops foetalis: 2 2013: 7 deaths (7/93) – Extreme prematurity: 4 – Severe NEC :3

23. Sepsis Sepsis (1 Coagulase negative staphylococci12 Gram negative bacilli3 Other gram positive cocci4 No sepsis due to lacto bacilli and bifido bacterium

24. 20132014 Antenatal steroids86.3%91.8% Any human milk on discharge50.6%58.5% Only human milk on discharge32.9%34% Small for gestational age27.8%28.2% Probiotics54.4%84.9% NEC13.9%1.9% Sepsis17% 2013-14 VON annual reports for Newport

25. Summary Probiotics has become part of feeding protocol in VLBW infants in our unit Feasible to prescribe and give probiotics Safe and no side effects reported so far in our unit Outcome data too early to interpret

26. ? Questions