Introducing a new practice on the NICU: Probiotics

Introducing a new practice onthe NICU: Probiotics

A James1

H Tranter2

A Davies1

S Cherian2

Royal Gwent Hospital1 &

University Hospital of Wales2

lactobacillus-acidophilus-original-strain-317-402-narine.jpg

Background

•Necrotizing enterocolitis (NEC) is a major cause ofmorbidity and mortality in preterm infants

•Affects 6-7% of VLBW infants

•Economic burden of NEC is significant

•Probiotics are live micro-organisms whenadministered in adequate amounts confer a healthbenefit on the host

–Improved gut barrier

–Enhanced mucosal IgA response

–Increased production of antiinflammatory cytokines

Reducing the risk of NEC anddeath in preterm infants

Shlomai NO et al Neonatology 2014

Probiotics for infants < 1500 g:Preventing severe NEC (stage II-III)

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NNT 25

AlFaleh et al Cochrane Reviews 2014

Probiotics for infants < 1500 g:Reducing mortality

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NNT 33

AlFaleh et al Cochrane Reviews 2014

Species of probiotic:Prevention of severe NEC

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Probiotic species:Reducing mortality

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Infloran

•Contains Lactobacillus acidophilus andBifidobacterium bifidus

•The most widely studied product

•Babies receive a daily dose of 109 of each livebacterial species

•Not licensed as a medicine, categorised as asupplement in UK

•Low cost intervention- approx £1 pertreatment per day per baby

Introducing change

•Literature review, discussions within units

•Microbiology: Drug samples obtained, cultured

•Public Health, IPCNG: discussions, review

•Pharmacy, Medicines group: discussions, review

•Presented to Directorate Clinical Governance

•Business case, presented to Trust Finance

•Guidelines prepared, PIL prepared

•Staff education

Cost of Infloran

•Estimated number of infants: 70

•Estimated median duration:7 weeks

•Cost per capsule: £0.90

•Cost per patient: £44.10

•Cost per year: £3087

Cost of treating NEC

•Increased direct hospital cost:

•‘Medical’ NEC: $ 14,000

•‘Surgical NEC’: $23,000

•Estimated 5cases/year/unit: $80,000/£50,000

•NB: 2009 CPI, USA

Johnson T et al J Pediatrics 2013

Collaboration

•PINC UK: Probiotics In Newborns Collaboration

•Newcastle, Bradford, Norfolk & Norwich

•Eligible infants: <32 weeks gestation

<1500g birth weight

< 7 days old if outborn, no NEC

PINC UK

•Study period: 01/05/2013- 30/04/2014

•Control period: 01/05/2012-30/04/2013

Infloran prescription

•Infloran: 109 bacilli LBA and BBB in 250mg

•Dose is 125mg twice daily

•Quality control data available

•MHRA no objection to use in a hospital setting

•Prescribed as drug for quality control andsafety reasons

•Pharmacy procures, maintains cold chain

Preparation & administration

•Preparation in designated area in milk kitchen

•Capsule contents dissolved in 1ml water, 0.5mladministered as a bolus

•Can be started when feeds of 0.5ml tolerated

•Not to be administered if on continuous feeds

•Consider stopping if unwell, feeds stopped

• Safe to administer if on steroids

Results: Eligible infants

Study group

Control group

Number

164

170

Gestation median (full range) weeks

30 (23-37)

29 (23-39)

Birth weight median (full range) grams

1270 (420-2370)

1223 (520-2170)

Study group

•Probiotics received130

•Age at start (Median)5 days

• Age at start (Min)1 day

• Age at start (Max)58 days

Study group

•Duration of administration of probiotics:

•Median17 days

•Min1 day

•Max65 days

Outcomes

Study group (n=164)

Control group (n=170)

Probiotics given

130

NEC ≥ stage2*

Deaths (all causes)*

Positive blood cultures*

*Fishers exact test NS

Reason fornon-administration

•Died before starting feeds8

•Transferred out before feeds started4

•>34 weeks when feeds started9

•>34 weeks on 01/05/20133

•Missed10

Cause of death

Study

•Extensive NEC6

•Sepsis2

•Complications of prematurity7

•Congenital anomalies1

•Twin to twin transfusion1

Control

•Extensive NEC 4

•Sepsis 1

•Complications of prematurity10

Newport, Cardiff:Study group

Newport (n=93)

Cardiff (n=71)

Probiotics given

NEC ≥ stage2

Deaths (all causes)

Reducing the risk of NEC anddeath in preterm infants

Shlomai NO et al Neonatology 2014

✓

Confounding factors

Newport (%)

Cardiff (%)

VONNetwork(%)

Antenatal steroids

86.3

86.6

82.9

Any human milk on discharge

43.3

47.5

57.3

Only human milk on discharge

12.5

11.7

Ibuprofen for PDA

1.6

8.1

Major congenital anomalies

1.7

10.4

4.4

Small for gestational age

30.5

35.8

24.7

NEC

13.9

1.6

4.5

2013 VON Annual reports for Newport and Cardiff

? Differences in population, microbiome

NEC in Japan

• Incidence 0.2%-1.6%: ? reason

• Exclusive breast milk <28 w infants

• Full feeds in 7 days

• Avoid UVC insertion

• Early use of PIC lines

• Probiotics

• Minimal handling

• Use antibiotics only if certain of infections

Isayama T et al Pediatrics 2012

Lee SK at SIGNEC 2014

EPIQ Canada

•Evidence Based Practice for Improving Quality

• All tertiary NICUs in Canada

• Included all infants <29w gestation

• For reducing NEC: practice changes implemented

–Standardised feeding guidelines

– Early feeding

– Use of donor milk

–Colostrum & enhanced breast milk feeds

– Early TPN

– Hold enteral feeds during blood transfusions

Lee SK CMAJ 2014

EPIQ Canada

•NEC reduced significantly

•Pre: Post intervention: 10% vs 8%, OR 0.73 (.52-.98)

• Effective practices were:

–Standardised feeding guidelines

– Early feeding

–Use of donor milk

–Colostrum & enhanced breast milk feeds

– Early TPN

– Hold enteral feeds during blood transfusions

Lee SK CMAJ 2014

Conclusions

•Introduced routine probiotic use on 2 NICUs

•Safe: No sepsis with probiotic organism

•No difference in NEC, sepsis or death

•Small numbers

•Need to improve breast feeding both centers

•? Consider holding enteral feeds duringtransfusions at Cardiff (TANEC audit)