Table 1 Studies included in the systematic review and meta-analysis

Al-Hosni, 2012 [33]

P

Preterm infants with BW 501–1000 g, appropriate for gestational age, and ≤ 14 days of age at time of feeding initiation

Lactobacillus rhamnosus GG LGG

Non specified

Extra milk

DB

Bifidobacterium infantis

R

D: 0.5 × 10⁹ CFU each probiotic, OD

C

S: first enteral feeding

Multic.

E: discharge or until 34 w postmenstrual age

Bin-Nun, 2005 [40]

P

Preterm infants with BW < 1500 g, who began enteral feeding on a weekday

Bifidobacterium infantis

OMM, PFM

HM or FM

B

Streptococcus thermophilus

R

Bifidobacterium bifidus

C

D: 0.35 × 10⁹ CFU each probiotic, OD

S: start of enteral feeding

E: 36 w postconceptual age

Braga, 2011 [35]

P

Inborn infants with BW 750–1499 g

Lactobacillus casei

HM

Extra HM

DB

Bifidobacterium breve

R

D: 3.5 × 10⁷ CFU to 3.5 × 10⁹ CFU OD

C

S: day 2

E: day 30, NEC diagnosis, discharge, death, whichever occurred first

Costalos, 2003 [49]

P

GA 28–32 w

Saccharomyces boulardii

PFM

MDX

R

No major GI problem

D: 1 × 10⁹ CFU BD

C

Not receiving antibiotics

S: non-specified

Not receiving breast milk

Median duration of probiotic supplementation: 30 days

Dani, 2002 [42]

P

Infants with GA < 33 w or BW < 1500 g

Lactobacillus rhamnosus GG

OMM, DM or FM

MDX

DB

D: 6 × 10⁹ CFU OD

R

S: first feed

C

E: discharge

Multic.

Demirel, 2013 [28]

P

Preterm infants with GA ≤ 32 w and BW ≤ 1500 g, who survived to feed enterally

Saccharomyces boulardii

HM, FM

None

B

D: 5 × 10⁹ CFU OD

R

S: first feed

C

E: discharge

Dilli, 2015 [44]

P

Preterm infants with GA <32 weeks and BW <1500 g, born at or transferred to the NICU within the first week of life and fed enterally before inclusion

Bifidobacterium

HM, FM

MDX powder

DB

Lactis

R

D: 5 × 10⁹ CFU

C

S: beyond d7 after birth

Multic.

E: death or discharge (max 8 weeks)

Fernández-Carrocera, 2013 [32]

P

Preterm infants with BW < 1500 g

Lactobacillus acidophilus 1 CFU/g

OMM, PFM

None

DB

Infants with NEC IA and IB were excluded

Lactobacillus rhamnosus 4.4 × 10⁸ CFU/g

R

Lactobacillus casei 1 × 10⁹ CFU/g

C

Lactobacillus plantarum 1.76 × 10⁸ CFU/g

Bifidobacterium infantis 2.76 × 10⁷ CFU/g

Streptococcus thermophilus 6.6 × 10⁵ CFU/g

Total D: 1 g powder OD

S: start of enteral feeding

E: non-specified

Jacobs, 2013 [26]

P

Preterm infants with GA <32 w and BW < 1500 g

Bifidobacterium infantis BB-02 300 CFU × 10⁶

HM, FM

MDX powder

DB

Streptococcus thermophilus Th-4 350 CFU × 10⁶

R

Bifidobacterium lactis BB-12 350 CFU × 10⁶

C

Total D: 1 × 10⁹ CFU × 1.5 g maltodextrin powder OD

Multic.

S: enteral feed ≥ 1 ml every 4 h

E: discharge or term corrected age

Kitajima, 1997 [52]

P

Preterm infants with BW < 1500 g

Bifidobacterium breve YIT4010

OMM, FM after full enteral feeding had been reached

Distilled water

R

D: 0.5 × 10⁹ CFU OD

C

S: within 24 h of life

Duration of probiotic supplementation: 28 days

Lin, 2005

P

Infants with BW < 1500 g, who started to feed enterally and survived beyond day 7

Lactobacillus acidophilus

OMM, DM

None

M

Bifidobacterium infantis

R

D: ≥ 10⁶ CFU each probiotic (=125 mg/kg), BD

C

S: start of enteral feeding

E: discharge

Lin, 2008

P

Preterm infants with GA < 34 w and BW ≤ 1500 g, who survived to feed enterally

Lactobacillus acidophilus NCDO 1746

HM, FM

None

B

Bifidobacterium bifidum NCDO 1453

R

D: 1 × 10⁹ CFU each probiotic (=125 mg/kg) BD

C

S: day 2 of age

Multic.

Duration: 6 weeks

Manzoni, 2006 [37]

P

Infants with BW < 1500 g, ≥ 3 days of life, who started enteral feeding with HM

Lactobacillus rhamnosus LGG

OMM, DM

None

DB

D: 6 × 10⁹ CFU/day

R

S: day 3 of life

C

E: end of the 6th week or discharge

Mihatsch, 2010 [43]

P

Preterm infants with GA < 30 w and BW ≤ 1500 g

Bifidobacterium lactis BB12

HM, PFM

Indistinguishable powder

R

D: 2 × 10⁹ CFU/kg 6 times a day

C

S: start of enteral feeding

E: non-specified

Mohan, 2006 [53]

P

Preterm infants (GA < 37 w)

Bifidobacterium lactis BB12

FM

Not stated

DB

D: 1.6 × 10⁹ CFU on day 1 to 3, and 4.8 × 10⁹ CFU from day 4 onwards

R

S: first day of life

C

Duration: 21 days

Oncel, 2013 [25]

P

Preterm infants with GA ≤ 32 w and BW ≤ 1500 g, who survived to feed enterally

Lactobacillus reuteri DSM 17938

HM, FM

Oil base

DB

D: 1 × 10⁸ CFU OD

R

S: first feed

C

E: death or discharge

Patole, 2014 [45]

P

Preterm infants with GA < 33 w and BW < 1500 g

Bifidobacterium breve M16-V

HM, FM

Dextrin

DB

D: 3 × 10⁹ CFU OD (1.5 × 109 CFU OD for newborns ≤ 27 w until they reached 50 ml/kg/day enteral feeds)

R

S: start of enteral feed

C

E: corrected age of 37 w

Rojas, 2012 [30]

P

Preterm infants with BW ≤ 2000 g, hemodynamically stable, ≤ 48 h of age (regardless start of enteral feeding)

Lactobacillus reuteri DSM 17938

HM, FM

Oil base

DB

D: 1 × 10⁸ CFU OD

R

S: age ≤ 48 h

C

E: death or discharge

Multic.

Rougé, 2009 [50]

P

Preterm infants with GA < 32 w and BW < 1500 g, ≤ 2 w of age, without any disease other than those linked to prematurity, who started enteral feeding before inclusion

Bifidobacterium longum BB536

OMM, DM or PFM

MDX

DB

Lactobacillus rhamnosus GG BB536-LGG

R

Total D: 1 × 10⁸ CFU/day

C

S: start of enteral feeding

Bic.

E: discharge

Roy, 2014 [58]

P

Preterm infants (GA < 37w) and BW < 2500 g, with stable enteral feeding within 72 h of birth

Lactobacillus acidophilus 1.25 × 10⁹ CFU × 1 g

HM

Sterile water

DB

B. longum 0.125 × 10⁹ CFU × 1 g

R

B. bifidum 0.125 × 10⁹ CFU × 1 g

C

B. lactis 1 × 10⁹ CFU × 1 g

D: half a 1 g sachet

S: from 72 h of life

E: after 6 w or at discharge

Saengtawesin, 2014 [48]

P

Preterm infants with GA ≤ 34 w and BW ≤ 1500 g

Lactobacillus acidophilus 1 × 10⁹ CFU

HM, PFM

None

R

Bifidobacterium

C

bifidum 1 × 10⁹ CFU

D: 125 mg/kg BD

S: start of feeding

E: 6 w of age or discharge.

Samanta, 2009

P

Preterm infants with GA < 32 w and BW < 1500 g, who started enteral feeding and survived beyond 48 h of age

Bifidobacterium infantis

HM

None

DB

Bifidobacterium bifidum

R

Bifidobacterium longum

C

Lactobacillus acidophilus

D: 2.5 × 10⁹ CFU each probiotic, BD

S: start of enteral feeding

E: discharge

Sari, 2011 [34]

P

Preterm infants with GA < 32 w or BW < 1500 g, who survived to feed enterally

Lactobacillus sporogenes

HM, FM

None

B

D: 0.35 × 10⁹ CFU OD

R

S: first feed

C

E: discharge

Serce, 2013 [27]

P

Preterm infants with GA ≤ 32 w and BW ≤ 1500 g, who survived to feed enterally

Saccharomyces boulardii

HM, FM

Distilled water

M

D: 0.5 × 10⁹ CFU/kg BD

R

S: non-specified

C

E: non-specified

Stratiki, 2007 [39]

P

Preterm infants with GA 27–32 w, formula-fed, without major congenital anomalies

Bifidobacterium lactis

FM

None

B

D: 2 × 10⁷ CFU/g of milk powder

R

S: start of enteral feeding

C

E: non-specified

Totsu, 2014 [46]

P

Infants with BW < 1500 g

Bifidobacterium bifidum

HM, FM

Dextrin

DB

D: 2.5 × 10⁹ CFU, divided in two doses

CLR

S: within 48 h after birth

C

E: body weight 2000 g

Multic.